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Agrawal M, Chowhan AK. Paediatric renal tumors: An insight into molecular characteristics, histomorphology and syndromic association. World J Nephrol 2025; 14:99380. [DOI: 10.5527/wjn.v14.i2.99380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2024] [Revised: 12/19/2024] [Accepted: 01/14/2025] [Indexed: 04/09/2025] Open
Abstract
Paediatric renal tumors are rare and accounts for about 7% of all paediatric malignant tumors. The spectrum of paediatric renal tumors ranges from benign to malignant. Benign tumors include cystic nephroma, metanephric tumors and ossifying renal tumor of infancy. Tumor with low grade malignancy includes mesoblastic nephroma. Malignant tumors are nephroblastoma, clear cell sarcoma, malignant rhabdoid tumor, anaplastic sarcoma and Ewing sarcoma. Additionally, there are molecularly defined renal tumors, which includes renal cell carcinoma (RCC) with MiT translocations, ALK-rearranged RCC, eosinophilic solid and cystic RCC and SMARCB1- deficient renal medullary carcinoma. These tumors apart from having characteristic clinical presentation and histomorphology, also carry typical molecular mutations and translocations. Certain renal tumors have association with various genetic syndromes such as Beckwith-Weidmann syndrome, Wilm’s tumor, aniridia, genitourinary anomalies and mental retardation syndrome, Denys-Drash syndrome, rhabdoid tumor predisposition syndrome and DICER syndrome. This review article focusses on molecular characteristics, histomorphology and syndromic association of pediatric renal tumors, their immunohistochemical approach to diagnosis with recent updates in molecularly defined renal tumors.
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Affiliation(s)
- Mousmi Agrawal
- Department of Pathology and Lab Medicine, All India Institute of Medical Sciences (AIIMS), Raipur 492099, Chhattisgarh, India
| | - Amit K Chowhan
- Department of Pathology and Lab Medicine, All India Institute of Medical Sciences (AIIMS), Raipur 492099, Chhattisgarh, India
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2
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Perotti D, O'Sullivan MJ, Walz AL, Davick J, Al-Saadi R, Benedetti DJ, Brzezinski J, Ciceri S, Cost NG, Dome JS, Drost J, Evageliou N, Furtwängler R, Graf N, Maschietto M, Mullen EA, Murphy AJ, Ortiz MV, van der Beek JN, Verschuur A, Wegert J, Williams R, Spreafico F, Geller JI, van den Heuvel-Eibrink MM, Hong AL. Hallmark discoveries in the biology of non-Wilms tumour childhood kidney cancers. Nat Rev Urol 2025:10.1038/s41585-024-00993-6. [PMID: 39881003 DOI: 10.1038/s41585-024-00993-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/17/2024] [Indexed: 01/31/2025]
Abstract
Approximately 20% of paediatric and adolescent/young adult patients with renal tumours are diagnosed with non-Wilms tumour, a broad heterogeneous group of tumours that includes clear-cell sarcoma of the kidney, congenital mesoblastic nephroma, malignant rhabdoid tumour of the kidney, renal-cell carcinoma, renal medullary carcinoma and other rare histologies. The differential diagnosis of these tumours dates back many decades, when these pathologies were identified initially through clinicopathological observation of entities with outcomes that diverged from Wilms tumour, corroborated with immunohistochemistry and molecular cytogenetics and, subsequently, through next-generation sequencing. These advances enabled near-definitive recognition of different tumours and risk stratification of patients. In parallel, the generation of new renal-tumour models of some of these pathologies including cell lines, organoids, xenografts and genetically engineered mouse models improved our understanding of the development of these tumours and have facilitated the identification of new therapeutic targets. Despite these many achievements, paediatric and adolescent/young adult patients continue to die from such rare cancers at higher rates than patients with Wilms tumour. Thus, international coordinated efforts are needed to answer unresolved questions and improve outcomes.
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Affiliation(s)
- Daniela Perotti
- Predictive Medicine: Molecular Bases of Genetic Risk, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy
| | - Maureen J O'Sullivan
- Histology Laboratory, Children's Health Ireland at Crumlin, Dublin, Ireland
- Histopathology, School of Medicine, Trinity College, Dublin, Ireland
- Departments of Histopathology and Paediatrics, School of Medicine, Trinity College Dublin, Dublin, Ireland
| | - Amy L Walz
- Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - Jonathan Davick
- University of Iowa Hospitals and Clinics Stead Family Children's Hospital, Carver College of Medicine, Iowa City, IA, USA
| | - Reem Al-Saadi
- UCL Great Ormond Street Institute of Child Health, University College London, London, UK
| | - Daniel J Benedetti
- Division of Pediatric Hematology/Oncology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Jack Brzezinski
- Division of Haematology/Oncology, Hospital for Sick Children, Toronto, Ontario, Canada
- Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada
| | - Sara Ciceri
- Predictive Medicine: Molecular Bases of Genetic Risk, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy
| | - Nicholas G Cost
- Department of Surgery, Division of Urology, University of Colorado School of Medicine and the Surgical Oncology Program at Children's Hospital Colorado, Denver, CO, USA
| | - Jeffrey S Dome
- Division of Oncology, Center for Cancer and Blood Disorders, Children's National Hospital, Washington, DC, USA
- Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC, USA
| | - Jarno Drost
- Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
- Oncode Institute, Utrecht, the Netherlands
| | | | - Rhoikos Furtwängler
- Pediatric Hematology and Oncology, Children's Hospital, Inselspital Bern University, Bern, Switzerland
- Childhood Renal Tumour Center Saarland University, Homburg, Germany
| | - Norbert Graf
- Department Paediatric Oncology & Hematology, Saarland University, Homburg, Germany
| | | | - Elizabeth A Mullen
- Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA, USA
| | - Andrew J Murphy
- St. Jude Children's Research Hospital Memphis, Memphis, TN, USA
| | | | - Justine N van der Beek
- Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
- University Medical Center Utrecht, Utrecht, the Netherlands
| | - Arnauld Verschuur
- Department of Pediatric Hematology and Oncology, Hôpital d'Enfants de la Timone, APHM, Marseille, France
| | - Jenny Wegert
- Theodor-Boveri-Institute/Biocenter, Developmental Biochemistry, Wuerzburg University, Wuerzburg, Germany
| | - Richard Williams
- Developmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London, London, UK
- Section of Genetics and Genomics, Faculty of Medicine, Imperial College London, London, UK
| | - Filippo Spreafico
- Paediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy
| | - James I Geller
- Division of Oncology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA
| | | | - Andrew L Hong
- Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
- Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, GA, USA.
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Sudour-Bonnange H, van Tinteren H, Ramírez-Villar GL, Godzinski J, Irtan S, Gessler M, Chowdhury T, Audry G, Fuchs J, Powis M, van de Ven CP, Okoye B, Smeulders N, Vujanic GM, Verschuur A, L'Herminé-Coulomb A, de Camargo B, de Aguirre Neto JC, Schenk JP, van den Heuvel-Eibrink MM, Pritchard-Jones K, Graf N, Bergeron C, Furtwängler R. Characteristics and outcome of synchronous bilateral Wilms tumour in the SIOP WT 2001 Study: Report from the SIOP Renal Tumour Study Group (SIOP-RTSG). Br J Cancer 2024; 131:972-981. [PMID: 39080350 PMCID: PMC11405756 DOI: 10.1038/s41416-024-02799-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Revised: 07/02/2024] [Accepted: 07/09/2024] [Indexed: 09/18/2024] Open
Abstract
BACKGROUND Among patients with nephroblastoma, those with bilateral disease are a unique population where maximising tumour control must be balanced with preserving renal parenchyma. METHODS The SIOP 2001 protocol recommended surgery after neoadjuvant cycle(s) of Dactinomycin and Vincristine (AV) with response-adapted intensification, if needed. Adjuvant treatment was given based on the lesion with the worst histology. RESULTS Three hundred and twenty seven patients with stage V disease were evaluable: 174 had bilateral Wilms tumour (BWT), 101 unilateral WT and contralateral nephroblastomatosis (NB) and 52 bilateral nephroblastomatosis. In these three groups, the estimated 5y-EFS was 76.1%, 84.6%, and 74.9%, respectively. AV chemotherapy alone was the successful chemotherapy for 58.7% of all the patients and 65.6% of the non-metastatic patients. Among the 174 patients with BWT, 149 (88.2%) had at least one nephron-sparing surgery. Twenty of 61 bilateral stage I patients were treated with four-week AV postoperatively achieving 94.4% 5y-EFS. At last follow-up, 87% of patients had normal renal function. CONCLUSIONS This study demonstrates that AV without anthracyclines is sufficient to achieve NSS and good survival in the majority of patients. For patients with bilateral stage I WT and intermediate risk histology, only four weeks adjuvant AV seems to be sufficient. CLINICAL TRIAL REGISTRATION NCT00047138.
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Affiliation(s)
| | - Harm van Tinteren
- Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands
| | - Gema L Ramírez-Villar
- Department of Pediatric Oncology, Hospital Universitario Virgen Del Rocio, Sevilla, Spain
| | - Jan Godzinski
- Department of Pediatric Surgery, Marciniak Hospital, Fieldorfa 2 and Department of Pediatric Traumatology and Emergency Medicine, Wroclaw Medical university, Wrocław, Poland
| | - Sabine Irtan
- Department of Pediatric Surgery, Hospital Trousseau, Paris, France
| | - Manfred Gessler
- Theosor-Boveri Institute/Biocenter and Comprehensive Cancer Center Mainfranken, University of Wuerzburg, Würzburg, Germany
| | - Tanzina Chowdhury
- Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK
| | - Georges Audry
- Department of Pediatric Surgery, Hospital Trousseau, Paris, France
| | - Joerg Fuchs
- Department of Pediatric Surgery and Urology, University Hospital Tübingen, 72076, Tuebingen, Germany
| | - Mark Powis
- Department of Pediatric Surgery, Leeds Teaching Hospital NHS Trust, Leeds, UK
| | | | - Bruce Okoye
- Department of Paediatric Surgery, St George's University Hospital, London, UK
| | - Naima Smeulders
- Great Ormond Street Hospital for Children NHS Foundation Trust, London, WC1N 3JH, UK
| | - Gordan M Vujanic
- Department of Pathology, Sidra Medicine and weill Cornell Medicine- Qatar, Doha, Qatar
| | - Arnaud Verschuur
- Department of Pediatric Hemato-Oncology, Hospital La Timone, Marseille, France
| | | | - Beatriz de Camargo
- Pediatric Hematology and Oncology program, research Center, Instituto National de Cancer, Rio de Janeiro, Brazil
| | | | - Jens Peter Schenk
- Sektion Pädiatrische Radiologie, Klinik für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Heidelberg, Heidelberg, Deutschland
| | - Mary M van den Heuvel-Eibrink
- Princess Maxima Center for Pediatric Oncology, Utrecht, The Netherlands
- Division of Childhealth, Wilhelmina Children's Hospital, Utrecht, the Netherlands
| | - Katy Pritchard-Jones
- Developmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London, London, UK
| | | | - Christophe Bergeron
- Department of Pediatric Oncology and Hematology, Centre Léon Berard, Lyon, France
| | - Rhoikos Furtwängler
- Saarland University, Homburg, Germany
- Division of Pediatric Hematology and Oncology, Department of Pediatrics, Inselspital, University Bern, Bern, Switzerland
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Zhang A, Yuan X, Jiang S, Xu D, Huang C, Tang JY, Gao Y. Outcomes of children with clear cell sarcoma of kidney following NWTS strategies in Shanghai China (2003-2021). PLoS One 2024; 19:e0306863. [PMID: 38980838 PMCID: PMC11233012 DOI: 10.1371/journal.pone.0306863] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2023] [Accepted: 06/24/2024] [Indexed: 07/11/2024] Open
Abstract
BACKGROUND Although clear cell sarcoma of kidney (CCSK) is rare, it is the second most common renal tumor in children after Wilms' tumor. NWTS and SIOP are two major groups which had made tremendous efforts on renal tumors, but the strategies are different, for NWTS follows the upfront surgery principle providing definite pathology and the SIOP follows the upfront chemotherapy principle, each has its own advantages. Here we aimed to evaluate the outcomes of CCSK in China following NWTS strategies to analyze the prognostic factors. METHODS For this multicenter retrospective study, a total of 54 patients were enrolled from three children's hospitals, between April 2003 and December 2021. Treatment comprised upfront radical nephrectomy, followed by radiotherapy and intensive chemotherapy. Clinical records were regularly updated. Prognostic factors and survival rates were evaluated. RESULTS The 54 enrolled patients had a median age of 37 months (range, 4 months to 11.4 years). The stage distribution was 16% stage I (n = 9), 30% stage II (n = 16), 39% stage III (n = 21), and 15% stage IV (n = 8). Among stage IV, metastasis sites included the lung (n = 6), bone (n = 1), and intra-orbital/cervical lymph node (n = 1). After a median follow-up of 5.6 years, the 5-year event-free survival (EFS) was 82.4±5.4%, and overall survival was 88.1±4.6%. The EFS was 100% for stage I, 93.8 ±6.1% for stage II, 71.1±10.0% for stage III, and 68.6±18.6% for stage IV. Univariate analysis revealed that staging (III/IV), tumor rupture, and inferior vena cava tumor thrombus were inferior prognostic factors. Multivariate analysis revealed that tumor rupture was independent poor prognostic factor (P = 0.01, HR 5.9). Among relapsed patients, relapse occurred a median of 11 months after diagnosis (range, 4-41 months), and 50% (4/8) achieved a second complete remission after multiple treatment. None of the six lung metastasis patients received lung RT, only one patient developed a relapse and was salvaged by RT after relapse. CONCLUSIONS Tumor rupture was independent poor prognostic factor. Upfront surgery of NWTS strategies can make a definite pathology diagnosis, but how to reduce tumor rupture during surgery is important especially in developing countries. The outcomes of patients with stage I-III CCSK in China were comparable to findings in other developed countries. Better outcomes were achieved in stage IV CCSK by using an intensive chemotherapy regimen including carboplatin, which require further confirmation by AREN0321. Lung RT may be safely omitted in selected patients who achieve a compete radiographic response after 6 weeks of systemic treatment (including surgery). Treatment should be encouraged even in CCSK cases with metastasis and relapse.
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Affiliation(s)
- Anan Zhang
- Department of Hematology and Oncology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaojun Yuan
- Department of Pediatric Hematology and Oncology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Shayi Jiang
- Department of Hematology and Oncology, Children's Hospital of Shanghai, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Dongqing Xu
- Department of Pediatric Hematology and Oncology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Can Huang
- Department of Hematology and Oncology, Children's Hospital of Shanghai, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jing Yan Tang
- Department of Hematology and Oncology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yijin Gao
- Department of Hematology and Oncology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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5
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Benedetti DJ, Renfro LA, Tfirn I, Daw NC, Kalapurakal JA, Ehrlich PF, Khanna G, Perlman E, Warwick A, Gow KW, Paulino AC, Seibel NL, Grundy P, Fernandez CV, Geller JI, Mullen EA, Dome JS. Treatment and outcomes of clear cell sarcoma of the kidney: A report from the Children's Oncology Group studies AREN0321 and AREN03B2. Cancer 2024; 130:2361-2371. [PMID: 38396300 PMCID: PMC11162327 DOI: 10.1002/cncr.35266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Revised: 01/18/2024] [Accepted: 01/30/2024] [Indexed: 02/25/2024]
Abstract
BACKGROUND 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. METHODS Four-year EFS was analyzed for patients enrolled on AREN0321 and on those enrolled on AREN03B2 who received AREN0321 stage-appropriate chemotherapy. RESULTS 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. CONCLUSIONS 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 with advanced-stage disease (ClinicalTrials.gov identifiers NCT00335556 and NCT00898365).
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Affiliation(s)
- Daniel J Benedetti
- Division of Hematology/Oncology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Lindsay A Renfro
- Division of Biostatistics, University of Southern California, Los Angeles, California, USA
- Children's Oncology Group, Monrovia, California, USA
| | - Ian Tfirn
- Children's Oncology Group, Monrovia, California, USA
| | - Najat C Daw
- Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - John A Kalapurakal
- Department of Radiation Oncology, Northwestern University, Chicago, Illinois, USA
| | - Peter F Ehrlich
- Section of Pediatric Surgery, University of Michigan, Ann Arbor, Michigan, USA
| | - Geetika Khanna
- Department of Radiology and Imaging Sciences, Emory University, Children's Healthcare of Atlanta, Atlanta, Georgia, USA
| | - Elizabeth Perlman
- Department of Pathology and Laboratory Medicine, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Anne Warwick
- Department of Pediatrics, F. Edward Hébert School of Medicine, Uniformed Services University, Bethesda, Maryland, USA
| | - Kenneth W Gow
- Division of Pediatric General and Thoracic Surgery, Seattle Children's Hospital, University of Washington, Seattle, Washington, USA
| | - Arnold C Paulino
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Nita L Seibel
- Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Paul Grundy
- Division of Immunology, Hematology, Oncology, Palliative Care, and Environmental Interactions, University of Alberta, Edmonton, Alberta, Canada
| | - Conrad V Fernandez
- Division of Pediatric Hematology/Oncology, IWK Health Centre, Dalhousie University, Halifax, Nova Scotia, Canada
| | - James I Geller
- Division of Oncology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA
| | - Elizabeth A Mullen
- Department of Pediatric Hematology/Oncology, Dana-Farber Cancer Institute/Boston Children's Hospital, Boston, Massachusetts, USA
| | - Jeffrey S Dome
- Division of Oncology and Department of Pediatrics, Children's National Hospital and the George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, USA
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Welter N, Metternich G, Furtwängler R, Bayoumi A, Mergen M, Kager L, Vokuhl C, Warmann SW, Fuchs J, Meier CM, Melchior P, Gessler M, Wagenpfeil S, Schenk JP, Graf N. How to improve initial diagnostic accuracy of kidney tumours in childhood?-A non-invasive approach. Int J Cancer 2024; 154:1955-1966. [PMID: 38319190 DOI: 10.1002/ijc.34870] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 12/15/2023] [Accepted: 01/08/2024] [Indexed: 02/07/2024]
Abstract
Non-invasive differentiation of paediatric kidney tumours is particularly important in the SIOP-RTSG protocols, which recommend pre-operative chemotherapy without histological confirmation. The identification of clinical and tumour-related parameters may enhance diagnostic accuracy. Age, metastases, and tumour volume (TV) were retrospectively analysed in 3306 patients enrolled in SIOP/GPOH 9, 93-01, and 2001 including Wilms tumour (WT), congenital mesoblastic nephroma (CMN), clear cell sarcoma (CCSK), malignant rhabdoid tumour of the kidney (MRTK), and renal cell carcinoma (RCC). WT was diagnosed in 2927 (88.5%) patients followed by CMN 138 (4.2%), CCSK 126 (3.8%), MRTK 58 (1.8%) and RCC 57 (1.7%). CMN, the most common localized tumour (71.6%) in patients younger than 3 months of age, was diagnosed earliest and RCC the latest (median age [months]: 0 and 154, respectively) both associated with significantly smaller TV (median TV [mL]: 67.2 and 45.0, respectively). RCC occurred in >14% of patients older than 120 months or older than 84 months with TV <100 mL. Receiver operating characteristic analyses discriminated WT from CMN, RCC and MRTK regarding age (AUC = 0.976, 0.929 and 0.791) and TV (AUC = 0.768, 0.813 and 0.622). MRTK had the highest risk of metastasis (37.9%) despite young age, whereas the risk of metastasis increased significantly with age in WT. Age and TV at diagnosis can differentiate WT from CMN and RCC. MRTK must be considered for metastatic tumours at young age. Identification of CCSK without histology remains challenging. Combined with MRI-characteristics, including diffusion-weighted imaging, and radiomics and liquid biopsies in the future, our approach allows optimization of biopsy recommendations and prevention of misdiagnosis-based neoadjuvant treatment.
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Affiliation(s)
- Nils Welter
- Department of Paediatric Oncology and Haematology, Saarland University, Homburg, Germany
| | - Gregor Metternich
- Department of Paediatric Oncology and Haematology, Saarland University, Homburg, Germany
| | - Rhoikos Furtwängler
- Department of Paediatric Oncology and Haematology, Saarland University, Homburg, Germany
- Division of Pediatric Hematology and Oncology, Department of Pediatrics, Inselpital University Hospital, Bern, Switzerland
| | - Ahmed Bayoumi
- Department of Paediatric Oncology and Haematology, Saarland University, Homburg, Germany
- Department of Paediatric Oncology, Children's Cancer Hospital 57357, Cairo, Egypt
| | - Marvin Mergen
- Department of Paediatric Oncology and Haematology, Saarland University, Homburg, Germany
| | - Leo Kager
- St. Anna Children's Hospital, Department of Paediatrics, Medical University Vienna, Vienna, Austria
- St. Anna Children's Cancer Research Institute, Vienna, Austria
| | - Christian Vokuhl
- Section of Paediatric Pathology, Department of Pathology, University Hospital Bonn, Bonn, Germany
| | - Steven W Warmann
- Department of Paediatric Surgery and Urology, University Hospital Tübingen, Tübingen, Germany
- Pediatric Surgery, Charité University Hospital, Berlin, Germany
| | - Jörg Fuchs
- Department of Paediatric Surgery and Urology, University Hospital Tübingen, Tübingen, Germany
| | - Clemens-Magnus Meier
- Department of General Surgery, Visceral, Vascular and Paediatric Surgery, Saarland University, Homburg, Germany
| | - Patrick Melchior
- Department of Radiation Oncology, Saarland University, Homburg, Germany
| | - Manfred Gessler
- Developmental Biochemistry and Comprehensive Cancer Centre Mainfranken, Theodor-Boveri-Institute/Biocenter, University of Würzburg, Würzburg, Germany
| | - Stefan Wagenpfeil
- Institute for Medical Biometry, Epidemiology and Medical Informatics, Saarland University, Homburg, Germany
| | - Jens-Peter Schenk
- Division of Paediatric Radiology, Department for Diagnostic and Interventional Radiology, University Hospital Heidelberg, Heidelberg, Germany
| | - Norbert Graf
- Department of Paediatric Oncology and Haematology, Saarland University, Homburg, Germany
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7
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Jin H, Yin Y, Wang H, Cheng W. 18 F-FDG PET/CT in a Case of Clear Cell Sarcoma of the Kidney. Clin Nucl Med 2024; 49:468-469. [PMID: 38377388 DOI: 10.1097/rlu.0000000000005071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/22/2024]
Abstract
ABSTRACT 18 F-FDG PET/CT was performed in a 1-year-old girl who had a heterogeneous mass in the right abdominal cavity revealed by abdominal ultrasound. A heterogeneous mass with internal necrosis, cystic changes, and hemorrhage in the right kidney, accompanied by a slight increase of FDG uptake, was observed in FDG PET/CT. Malignant renal tumor was considered, and Wilms tumor was preferentially suspected. However, the mass was demonstrated as clear cell sarcoma of the kidney by histopathological examination.
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Affiliation(s)
- Hongfu Jin
- From the Department of Nuclear Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
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8
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Tsiflikas I. [Renal tumors in children and adolescents]. RADIOLOGIE (HEIDELBERG, GERMANY) 2024; 64:18-25. [PMID: 37947863 DOI: 10.1007/s00117-023-01238-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 10/23/2023] [Indexed: 11/12/2023]
Abstract
CLINICAL/METHODOLOGICAL ISSUE Diagnosis and therapy of renal tumors in children and adolescents are standardized by study protocols from major international societies. Imaging plays a central role, and in Europe patients between the ages of 6 months and 14 years with renal tumors are referred to neoadjuvant chemotherapy without histological confirmation according to the study protocol due to the frequency of Wilms tumor. STANDARD RADIOLOGIC METHODS Ultrasound is used worldwide as the primary investigative procedure for suspected renal tumors. In Europe, magnetic resonance imaging (MRI) has become established for more advanced diagnosis. In addition to differential diagnosis, staging is crucial for therapy. According to current protocol, this includes computed tomography (CT) of the thorax for the evaluation of pulmonary metastases. METHODOLOGICAL INNOVATIONS Diffusion-weighted MRI provides promising results for the differentiation of nephroblastoma subtypes in addition to improved detectability of tumor foci. However, sufficient evidence is lacking. PERFORMANCE Differentiation of Wilms tumor from the highly malignant non-Wilm tumors, such as malignant rhabdoid tumor and clear cell sarcoma of the kidney, remains inconclusive based on imaging alone. Differential diagnosis is, therefore, based on morphologic and epidemiologic criteria. ASSESSMENT The high degree of standardization in the diagnosis and treatment of renal tumors in children and adolescents has led to a significant improvement in prognosis. Overall survival of patients with Wilms tumor is currently over 90%.
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Affiliation(s)
- Ilias Tsiflikas
- Abteilung für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Deutschland.
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9
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Dávila Fajardo R, Raymakers-Janssen P, van Grotel M, van Wösten-van Asperen RM, Terhaard CH, Lilien MR, van den Heuvel-Eibrink MM, Janssens GO. Long-term nephrotoxicity in irradiated pediatric kidney tumor survivors: A systematic review. Pediatr Blood Cancer 2023; 70:e30624. [PMID: 37561390 DOI: 10.1002/pbc.30624] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 08/01/2023] [Accepted: 08/02/2023] [Indexed: 08/11/2023]
Abstract
OBJECTIVE Nephrotoxicity can occur as a side effect after treatment for kidney tumor in childhood. The use of radiotherapy (RT) has a potential additional effect. METHODS A systematic electronic literature search that combined childhood kidney cancer with different treatments and nephrotoxicity terms was performed in EMBASE. Studies were included based on the reporting of nephrotoxicity occurrence after treatment for kidney tumor during pediatric age, with 75% of participants being under the age of 25 years at the time of diagnosis, and having been treated with any type of kidney surgery, chemotherapy, and/or RT. RESULTS A pooled analysis did not show significant difference in estimated glomerular filtration rate between the group of patients who received RT compared with the group treated without RT (SMD -0.11 [95% CI -1.07-0.84] p = .733). CONCLUSION The current literature suggests that the use of RT does not have a significant impact on the decline of kidney function as independent factor.
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Affiliation(s)
- Raquel Dávila Fajardo
- Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands
- Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
| | | | | | | | - Christianus H Terhaard
- Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Marc R Lilien
- Department of Pediatric Nephrology, University Medical Center Utrecht, Utrecht, The Netherlands
| | | | - Geert O Janssens
- Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands
- Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
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10
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Libes J, Hol J, Neto JCDA, Vallance KL, Tinteren HV, Benedetti DJ, Villar GLR, Duncan C, Ehrlich PF. Pediatric renal tumor epidemiology: Global perspectives, progress, and challenges. Pediatr Blood Cancer 2023; 70 Suppl 2:e30343. [PMID: 37096796 DOI: 10.1002/pbc.30343] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Revised: 08/28/2022] [Accepted: 08/29/2022] [Indexed: 04/26/2023]
Abstract
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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Affiliation(s)
- Jaime Libes
- Department of Pediatrics, University of Illinois College of Medicine, Peoria, Illinois, USA
| | - Janna Hol
- Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands
| | | | - Kelly L Vallance
- Hematology and Oncology, Cook Children's Medical Center, Fort Worth, Texas, USA
| | | | - Daniel J Benedetti
- Department of Pediatrics, Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Gema Lucia Ramirez Villar
- Hospital Universitario Virgen del Rocio, Pediatric Oncology Unit, University of Seville, Seville, Spain
| | - Catriona Duncan
- Great Ormond Street Hospital for Children (GOSH), NHS Foundation Trust, NIHR, Great Ormond Street Hospital Biomedical Research Centre, London, UK
| | - Peter F Ehrlich
- Department of Pediatric Surgery, C.S. Mott Children's Hospital, University of Michigan School of Public Health, Ann Arbor, Michigan, USA
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11
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Molecular Signature of Biological Aggressiveness in Clear Cell Sarcoma of the Kidney (CCSK). Int J Mol Sci 2023; 24:ijms24043743. [PMID: 36835166 PMCID: PMC9964999 DOI: 10.3390/ijms24043743] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Revised: 02/06/2023] [Accepted: 02/07/2023] [Indexed: 02/16/2023] Open
Abstract
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.
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12
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Walz AL, Maschietto M, Crompton B, Evageliou N, Dix D, Tytgat G, Gessler M, Gisselsson D, Daw NC, Wegert J. Tumor biology, biomarkers, and liquid biopsy in pediatric renal tumors. Pediatr Blood Cancer 2023; 70 Suppl 2:e30130. [PMID: 36592003 DOI: 10.1002/pbc.30130] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 11/10/2022] [Accepted: 11/12/2022] [Indexed: 01/03/2023]
Abstract
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.
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Affiliation(s)
- Amy L Walz
- Division of Hematology, Oncology, Neuro-Oncology, and Stem Cell Transplant, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA
| | - Mariana Maschietto
- Research Center, Boldrini Children's Hospital, Campinas, São Paulo, Brazil
| | - Brian Crompton
- Department of Pediatric Oncology, Dana-Farber/Harvard Cancer Center, Dana Farber Cancer Institute, Boston, Massachusetts, USA
| | - Nicholas Evageliou
- Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
| | - David Dix
- British Columbia Children's Hospital, Vancouver, British Columbia, Canada
| | - Godelieve Tytgat
- Princess Máxima Center for Pediatric Oncology, CS Utrecht, The Netherlands
| | - Manfred Gessler
- Comprehensive Cancer Center Mainfranken, Wuerzburg, Germany.,Theodor-Boveri-Institute/Biocenter, Developmental Biochemistry, University of Wuerzburg, Wuerzburg, Germany
| | - David Gisselsson
- Cancer Cell Evolution Unit, Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden
| | - Najat C Daw
- Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Jenny Wegert
- Theodor-Boveri-Institute/Biocenter, Developmental Biochemistry, University of Wuerzburg, Wuerzburg, Germany
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13
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Libes J, Hol J, Neto JCDA, Vallance KL, Tinteren HV, Benedetti DJ, Villar GLR, Duncan C, Ehrlich PF. Pediatric renal tumor epidemiology: Global perspectives, progress, and challenges. Pediatr Blood Cancer 2023; 70:e30006. [PMID: 36326750 DOI: 10.1002/pbc.30006] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Revised: 08/28/2022] [Accepted: 08/29/2022] [Indexed: 11/06/2022]
Abstract
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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Affiliation(s)
- Jaime Libes
- Department of Pediatrics, University of Illinois College of Medicine, Peoria, Illinois, USA
| | - Janna Hol
- Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands
| | | | - Kelly L Vallance
- Hematology and Oncology, Cook Children's Medical Center, Fort Worth, Texas, USA
| | | | - Daniel J Benedetti
- Department of Pediatrics, Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Gema Lucia Ramirez Villar
- Hospital Universitario Virgen del Rocio, Pediatric Oncology Unit, University of Seville, Seville, Spain
| | - Catriona Duncan
- Great Ormond Street Hospital for Children (GOSH), NHS Foundation Trust, NIHR, Great Ormond Street Hospital Biomedical Research Centre, London, UK
| | - Peter F Ehrlich
- Department of Pediatric Surgery, C.S. Mott Children's Hospital, University of Michigan School of Public Health, Ann Arbor, Michigan, USA
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14
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Koh KN, Han JW, Choi HS, Kang HJ, Lee JW, Yoo KH, Sung KW, Koo HH, Hong KT, Choi JY, Kang SH, Kim H, Im HJ, Hahn SM, Lyu CJ, Baek HJ, Kook H, Park KM, Yang EJ, Lim YT, Kim S, Lee JW, Chung NG, Cho B, Park M, Park HJ, Park BK, Lee JA, Park JE, Kim SK, Kim JY, Kim HS, Ma Y, Park KD, Park SK, Park ES, Shim YJ, Yoo ES, Ryu KH, Yoo JW, Lim YJ, Yoon HS, Lee MJ, Lee JM, Jeon IS, Jung HL, Chueh HW, Won S, The Korean Pediatric Hematology and Oncology Group (KPHOG). Epidemiologic and Clinical Outcomes of Pediatric Renal Tumors in Korea: A Retrospective Analysis of The Korean Pediatric Hematology and Oncology Group (KPHOG) Data. Cancer Res Treat 2023; 55:279-290. [PMID: 35952715 PMCID: PMC9873342 DOI: 10.4143/crt.2022.073] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Accepted: 08/07/2022] [Indexed: 02/04/2023] Open
Abstract
PURPOSE 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. MATERIALS AND METHODS From January 2001 to December 2015, data of pediatric patients (0-18 years) newly-diagnosed with renal tumors at 26 hospitals were retrospectively analyzed. RESULTS 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). CONCLUSION 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.
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Affiliation(s)
- Kyung-Nam Koh
- Division of Pediatric Hematology/Oncology, Department of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine, Seoul,
Korea
| | - Jung Woo Han
- Division of Pediatric Hematology and Oncology, Department of Pediatrics, Yonsei University College of Medicine, Seoul,
Korea
| | - Hyoung Soo Choi
- Department of Pediatrics, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam,
Korea
| | - Hyoung Jin Kang
- Department of Pediatrics, Seoul National University College of Medicine, Seoul,
Korea,Seoul National University Cancer Institute, Seoul,
Korea
| | - Ji Won Lee
- Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea
| | - Keon Hee Yoo
- Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea
| | - Ki Woong Sung
- Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea
| | - Hong Hoe Koo
- Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea
| | - Kyung Taek Hong
- Department of Pediatrics, Seoul National University College of Medicine, Seoul,
Korea,Seoul National University Cancer Institute, Seoul,
Korea
| | - Jung Yoon Choi
- Department of Pediatrics, Seoul National University College of Medicine, Seoul,
Korea,Seoul National University Cancer Institute, Seoul,
Korea
| | - Sung Han Kang
- Division of Pediatric Hematology/Oncology, Department of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine, Seoul,
Korea
| | - Hyery Kim
- Division of Pediatric Hematology/Oncology, Department of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine, Seoul,
Korea
| | - Ho Joon Im
- Division of Pediatric Hematology/Oncology, Department of Pediatrics, Asan Medical Center Children’s Hospital, University of Ulsan College of Medicine, Seoul,
Korea
| | - Seung Min Hahn
- Division of Pediatric Hematology and Oncology, Department of Pediatrics, Yonsei University College of Medicine, Seoul,
Korea
| | - Chuhl Joo Lyu
- Division of Pediatric Hematology and Oncology, Department of Pediatrics, Yonsei University College of Medicine, Seoul,
Korea
| | - Hee-Jo Baek
- Department of Pediatrics, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Gwangju,
Korea
| | - Hoon Kook
- Department of Pediatrics, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Gwangju,
Korea
| | - Kyung Mi Park
- Department of Pediatrics, Pusan National University School of Medicine, Yangsan,
Korea
| | - Eu Jeen Yang
- Department of Pediatrics, Pusan National University School of Medicine, Yangsan,
Korea
| | - Young Tak Lim
- Department of Pediatrics, Pusan National University School of Medicine, Yangsan,
Korea
| | - Seongkoo Kim
- Department of Pediatrics, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Jae Wook Lee
- Department of Pediatrics, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Nack-Gyun Chung
- Department of Pediatrics, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Bin Cho
- Department of Pediatrics, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul,
Korea
| | - Meerim Park
- Center for Pediatric Cancer, Department of Pediatrics, National Cancer Center, Goyang,
Korea
| | - Hyeon Jin Park
- Center for Pediatric Cancer, Department of Pediatrics, National Cancer Center, Goyang,
Korea
| | - Byung-Kiu Park
- Center for Pediatric Cancer, Department of Pediatrics, National Cancer Center, Goyang,
Korea
| | - Jun Ah Lee
- Department of Pediatrics, Korea Cancer Center Hospital, Seoul,
Korea
| | - Jun Eun Park
- Department of Pediatrics, Korea University School of Medicine, Seoul,
Korea
| | - Soon Ki Kim
- Department of Pediatrics, Inha University Hospital, Inha University College of Medicine, Incheon,
Korea
| | - Ji Yoon Kim
- Department of Pediatrics, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu,
Korea
| | - Hyo Sun Kim
- Department of Pediatrics, Inje University Haeundae Paik Hospital, Busan,
Korea
| | - Youngeun Ma
- Department of Pediatrics, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam,
Korea
| | - Kyung Duk Park
- Department of Pediatrics and Research Institute of Clinical Medicine of Jeonbuk National University-Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju,
Korea
| | - Sang Kyu Park
- Department of Pediatrics, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan,
Korea
| | - Eun Sil Park
- Department of Pediatrics, Gyeongsang National University School of Medicine, Jinju,
Korea
| | - Ye Jee Shim
- Department of Pediatrics, Keimyung University Dongsan Hospital, Keimyung University School of Medicine, Daegu,
Korea
| | - Eun Sun Yoo
- Department of Pediatrics, Ewha Womans University Seoul Hospital, Ewha Womans University College of Medicine, Seoul,
Korea
| | - Kyung Ha Ryu
- Department of Pediatrics, Ewha Womans University Seoul Hospital, Ewha Womans University College of Medicine, Seoul,
Korea
| | - Jae Won Yoo
- Department of Pediatrics, Chungnam National University College of Medicine, Daejeon,
Korea
| | - Yeon Jung Lim
- Department of Pediatrics, Chungnam National University College of Medicine, Daejeon,
Korea
| | - Hoi Soo Yoon
- Department of Pediatrics, Kyung Hee University College of Medicine, Seoul,
Korea
| | - Mee Jeong Lee
- Department of Pediatrics, Dankook University College of Medicine, Cheonan,
Korea
| | - Jae Min Lee
- Department of Pediatrics, Yeungnam University College of Medicine, Daegu,
Korea
| | - In-Sang Jeon
- Department of Pediatrics, Gachon University Gil Medical Center, Incheon,
Korea
| | - Hye Lim Jung
- Department of Pediatrics, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul,
Korea
| | - Hee Won Chueh
- Department of Pediatrics, Dong-A University College of Medicine, Busan,
Korea
| | - Seunghyun Won
- Medical Research Collaborating Center, Seoul National University Bundang Hospital, Seongnam,
Korea
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15
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Zhang M, Yao X, Guan X, Jia C, Zhang R, Wang H, Guo Y, Ni X, Yu Y, He L. Clinical relevance of BCOR internal tandem duplication and TP53 aberration in clear cell sarcoma of the kidney. Hum Pathol 2022; 134:45-55. [PMID: 36563883 DOI: 10.1016/j.humpath.2022.12.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 12/13/2022] [Accepted: 12/15/2022] [Indexed: 12/24/2022]
Abstract
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.
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Affiliation(s)
- Meng Zhang
- Department of Pathology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health (NCCH), Beijing, 100045, China
| | - Xingfeng Yao
- Department of Pathology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health (NCCH), Beijing, 100045, China
| | - Xiaoxing Guan
- Department of Pathology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health (NCCH), Beijing, 100045, China
| | - Chao Jia
- Department of Pathology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health (NCCH), Beijing, 100045, China
| | - Ruqian Zhang
- Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, MOE Key Laboratory of Major Diseases in Children, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health (NCCH), Beijing, 100045, China
| | - Huanmin Wang
- Department of Surgical Oncology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health (NCCH), Beijing, 100045, China
| | - Yongli Guo
- Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, MOE Key Laboratory of Major Diseases in Children, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health (NCCH), Beijing, 100045, China
| | - Xin Ni
- Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, MOE Key Laboratory of Major Diseases in Children, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health (NCCH), Beijing, 100045, China; Department of Otolaryngology, Head and Neck Surgery, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health (NCCH), Beijing, 100045, China; Biobank for Clinical Data and Samples in Pediatrics, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health (NCCH), Beijing, 100045, China
| | - Yongbo Yu
- Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, MOE Key Laboratory of Major Diseases in Children, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health (NCCH), Beijing, 100045, China; Biobank for Clinical Data and Samples in Pediatrics, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health (NCCH), Beijing, 100045, China.
| | - Lejian He
- Department of Pathology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health (NCCH), Beijing, 100045, China.
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16
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Ayaz E, Ozcan HN, Oguz B, Haliloglu M. Beyond Wilms tumor: imaging findings and outcomes of rare renal tumors in children. Pediatr Radiol 2022; 52:2557-2567. [PMID: 35760918 DOI: 10.1007/s00247-022-05422-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Revised: 05/10/2022] [Accepted: 06/02/2022] [Indexed: 10/17/2022]
Abstract
BACKGROUND Compared to Wilms, non-Wilms renal tumors in children are less well understood due to their rare occurrence which limits precise definition of the typical imaging patterns. OBJECTIVE This study aims to identify distinctive imaging findings, demographic characteristics and prognosis of pediatric non-Wilms renal tumors. MATERIALS AND METHODS From January 2007 to December 2018, 207 patients with a diagnosis of primary kidney neoplasia were yielded from our radiology archive, 171 of whom were diagnosed with Wilms tumor, 4 with angiomyolipoma and one with nephrogenic rest. The remaining 31 patients with a diagnosis of primary kidney neoplasia were enrolled in this retrospective study. Imaging data, age, gender, prognosis and findings regarding follow-up were noted. RESULTS Eight patients had renal cell carcinoma, seven had clear cell sarcoma, six had mesoblastic nephroma, four had rhabdoid tumor, three had desmoplastic small round cell tumor, two had cystic nephroma and one had metanephric stromal tumor. The age of diagnosis was > 8 years for renal cell carcinoma and desmoplastic small round cell tumor, < 5 years for rhabdoid tumor and < 7 months for mesoblastic nephroma. There was no gender preference for any tumor type. The prognosis for rhabdoid tumor was extremely poor in that all the patients followed up in our institute were deceased, whereas no recurrence was found in other tumors. Translocation type renal cell carcinoma had lower T2-weighted signal intensity, mesoblastic nephroma was a predominantly cystic mass, clear cell sarcoma was generally larger at presentation and extensive amorphous calcifications were seen in desmoplastic small round cell tumor. CONCLUSION For the differential diagnosis of pediatric non-Wilms renal tumors, age is the most important factor, followed by propensity to metastasize/aggressive behavior of the mass. Knowledge of specific imaging findings of these tumors may help to narrow the differential diagnosis.
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Affiliation(s)
- Ercan Ayaz
- Division of Pediatric Radiology, Department of Radiology, Hacettepe University School of Medicine, Sıhhiye, 06230, Ankara, Turkey. .,Department of Radiology, Diyarbakır Children's Hospital, Diyarbakır, Turkey.
| | - H Nursun Ozcan
- Division of Pediatric Radiology, Department of Radiology, Hacettepe University School of Medicine, Sıhhiye, 06230, Ankara, Turkey
| | - Berna Oguz
- Division of Pediatric Radiology, Department of Radiology, Hacettepe University School of Medicine, Sıhhiye, 06230, Ankara, Turkey
| | - Mithat Haliloglu
- Division of Pediatric Radiology, Department of Radiology, Hacettepe University School of Medicine, Sıhhiye, 06230, Ankara, Turkey
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17
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Schulpen M, Roy P, Wijnen MHWA, Tytgat GAM, van den Heuvel-Eibrink MM, van Tinteren H, Karim-Kos HE. Incidence and survival of paediatric renal tumours in the Netherlands between 1990 and 2014. Eur J Cancer 2022; 175:282-290. [PMID: 36174300 DOI: 10.1016/j.ejca.2022.08.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Revised: 08/09/2022] [Accepted: 08/17/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND This 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. METHODS Data 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. RESULTS The 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. CONCLUSIONS Incidence 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.
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Affiliation(s)
- Maya Schulpen
- Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
| | - Prakriti Roy
- Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
| | - Marc H W A Wijnen
- Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
| | | | | | - Harm van Tinteren
- Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands
| | - Henrike E Karim-Kos
- Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; Department of Research and Development, Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, the Netherlands.
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18
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Zhang Y, Chu Q, Ma Y, Miao C, Diao JJ. Overall survival nomogram and relapse-related factors of clear cell sarcoma of the kidney: A study based on published patients. Front Pediatr 2022; 10:943141. [PMID: 36186639 PMCID: PMC9523514 DOI: 10.3389/fped.2022.943141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Accepted: 07/25/2022] [Indexed: 11/17/2022] Open
Abstract
Background Rarity 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. Methods Patients 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. Result 256 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. Conclusion Our 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.
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Affiliation(s)
- Yuan Zhang
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
- Department of Pediatrics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Qian Chu
- Department of Preventive Treatment, District Second Hospital of Qingdao Huangdao of Traditional Chinese Medicine, Qingdao, China
| | - Yue Ma
- Guang'an men Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Chunshu Miao
- College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Juan-juan Diao
- Department of Pediatrics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
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Goh JY, Kuick CH, Sugiura M, Aw SJ, Zhao M, Tang H, Gunaratne S, Zhu F, Cai L, Teh BT, Thorner PS, Chang KTE. Paediatric
BCOR
‐associated sarcomas with a novel long spliced internal tandem duplication of
BCOR
exon 15. J Pathol Clin Res 2022; 8:470-480. [PMID: 35836306 PMCID: PMC9353662 DOI: 10.1002/cjp2.287] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 05/14/2022] [Accepted: 06/22/2022] [Indexed: 11/08/2022]
Abstract
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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Affiliation(s)
- Jian Yuan Goh
- Department of Pathology and Laboratory Medicine KK Women's and Children's Hospital Singapore
- Pathology Academic Clinical Programme SingHealth Duke‐NUS Medical School Singapore
| | - Chik Hong Kuick
- Department of Pathology and Laboratory Medicine KK Women's and Children's Hospital Singapore
| | - Masahiro Sugiura
- Department of Pathology and Laboratory Medicine KK Women's and Children's Hospital Singapore
| | - Sze Jet Aw
- Department of Pathology and Laboratory Medicine KK Women's and Children's Hospital Singapore
| | - Manli Zhao
- Department of Pathology The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health Hangzhou PR China
| | - Hongfeng Tang
- Department of Pathology The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health Hangzhou PR China
| | - Sandini Gunaratne
- Department of Pathology Lady Ridgeway Hospital for Children Colombo Sri Lanka
| | - Fucun Zhu
- Department of Pathology Fuzhou Children's Hospital of Fujian Province Fuzhou PR China
| | - Lin Cai
- Department of Pathology Fuzhou Children's Hospital of Fujian Province Fuzhou PR China
| | - Bin Tean Teh
- Laboratory of Cancer Epigenome National Cancer Centre Singapore Singapore
- Cancer and Stem Cell Biology Programme Duke‐NUS Medical School Singapore
| | - Paul S Thorner
- Department of Laboratory Medicine and Pathobiology University of Toronto Toronto ON Canada
| | - Kenneth Tou En Chang
- Department of Pathology and Laboratory Medicine KK Women's and Children's Hospital Singapore
- Pathology Academic Clinical Programme SingHealth Duke‐NUS Medical School Singapore
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20
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Roy P, van Peer SE, de Witte MM, Tytgat GAM, Karim-Kos HE, van Grotel M, van de Ven CP, Mavinkurve-Groothuis AMC, Merks JHM, Kuiper RP, Hol JA, Janssens GOR, de Krijger RR, Jongmans MCJ, Drost J, van der Steeg AFW, Littooij AS, Wijnen MHWA, van Tinteren H, van den Heuvel-Eibrink MM. Characteristics and outcome of children with renal tumors in the Netherlands: The first five-year's experience of national centralization. PLoS One 2022; 17:e0261729. [PMID: 35025887 PMCID: PMC8757983 DOI: 10.1371/journal.pone.0261729] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Accepted: 12/08/2021] [Indexed: 01/20/2023] Open
Abstract
Around 6% of all childhood malignancies represent renal tumors, of which a majority includes Wilms tumor (WT). Although survival rates have improved over the last decades, specific patients are still at risk for adverse outcome. In the Netherlands, since 2015, pediatric oncology care for renal tumors has been centralized in the Princess Máxima Center for Pediatric Oncology. Here, we describe experiences of the first 5 years of centralized care and explore whether this influences the epidemiological landscape by comparing data with the Netherlands Cancer Registry (NCR). We identified all patients <19 years with a renal mass diagnosed between 01-01-2015 and 31-12-2019 in the Princess Máxima Center. Epidemiology, characteristics and management were analyzed. We identified 164 patients (including 1 patient who refused consent for registration), in our center with a suspicion of a renal tumor. The remaining 163 cases included WT (n = 118)/cystic partially differentiated nephroblastoma (n = 2)/nephrogenic rests only (n = 6) and non-WT (n = 37). In this period, the NCR included 138 children, 1 17-year-old patient was not referred to the Princess Máxima Center. Central radiology review (before starting treatment) was performed in 121/163 patients, and central pathology review in 148/152 patients that underwent surgery. Treatment stratification, according to SIOP/EpSSG protocols was pursued based on multidisciplinary consensus. Preoperative chemotherapy was administered in 133 patients, whereas 19 patients underwent upfront surgery. Surgery was performed in 152 patients, and from 133 biomaterial was stored. Centralization of care for children with renal tumors led to referral of all but 1 new renal tumor cases in the Netherlands, and leads to referral of very rare subtypes not registered in the NCR, that benefit from high quality diagnostics and multidisciplinary decision making. National centralization of care led to enhanced development of molecular diagnostics and other innovation-based treatments for the future.
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Affiliation(s)
- Prakriti Roy
- Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
- * E-mail:
| | | | | | | | - Henrike E. Karim-Kos
- Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
- Department of Research and Development, Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, The Netherlands
| | | | | | | | | | - Roland P. Kuiper
- Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
- Department of Clinical Genetics, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands
| | - Janna A. Hol
- Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
| | - Geert O. R. Janssens
- Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
- Department of Radiation Oncology, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands
| | - Ronald R. de Krijger
- Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
- Department of Pathology, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands
| | - Marjolijn C. J. Jongmans
- Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
- Department of Clinical Genetics, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands
| | - Jarno Drost
- Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
- Oncode Institute, Utrecht, The Netherlands
| | | | - Annemieke S. Littooij
- Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht/Wilhelmina Children’s Hospital (UMCU), Utrecht, The Netherlands
| | | | - Harm van Tinteren
- Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
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21
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Yaguchi T, Kimura S, Sekiguchi M, Kubota Y, Seki M, Yoshida K, Shiraishi Y, Kataoka K, Fujii Y, Watanabe K, Hiwatari M, Miyano S, Ogawa S, Takita J. Description of longitudinal tumor evolution in a case of multiply relapsed clear cell sarcoma of the kidney. Cancer Rep (Hoboken) 2021; 5:e1458. [PMID: 34967151 PMCID: PMC8842696 DOI: 10.1002/cnr2.1458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 05/09/2021] [Accepted: 05/12/2021] [Indexed: 11/06/2022] Open
Abstract
Background Clear cell sarcoma of the kidney (CCSK) is the second most common pediatric renal tumor. Case A 2‐year‐old boy was diagnosed with CCSK, which relapsed four times until he yielded to the disease at the age of 7 years. To characterize the longitudinal genetic alterations occurring in the present case, we performed targeted‐capture sequencing by pediatric solid tumors panel (381 genes) for longitudinally sampled tumors, including autopsy samples of metastasis. Internal tandem duplication of BCOR (BCOR‐ITD) was the only truncal mutation, confirming the previously reported role of BCOR‐ITD in CCSK. Conclusion Acquisition of additional mutations along tumor relapses and detection of metastasis‐specific mutations were reminiscent of the tumor progression and therapeutic resistance of this case, leading to clonal selection and a dismal fate.
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Affiliation(s)
- Tomoki Yaguchi
- Department of Pediatrics, Graduate School of Medicine The University of Tokyo Tokyo Japan
| | - Shunsuke Kimura
- Department of Pediatrics, Graduate School of Medicine The University of Tokyo Tokyo Japan
- Department of Pediatrics, Graduate School of Biomedical Sciences Hiroshima University Hiroshima Japan
| | - Masahiro Sekiguchi
- Department of Pediatrics, Graduate School of Medicine The University of Tokyo Tokyo Japan
| | - Yasuo Kubota
- Department of Pediatrics, Graduate School of Medicine The University of Tokyo Tokyo Japan
| | - Masafumi Seki
- Department of Pediatrics, Graduate School of Medicine The University of Tokyo Tokyo Japan
| | - Kenichi Yoshida
- Department of Pathology and Tumor Biology, Graduate School of Medicine Kyoto University Kyoto Japan
| | - Yuichi Shiraishi
- Division of Cellular Signaling National Cancer Center Research Institute Tokyo Japan
| | - Keisuke Kataoka
- Department of Pathology and Tumor Biology, Graduate School of Medicine Kyoto University Kyoto Japan
| | - Yoichi Fujii
- Department of Pathology and Tumor Biology, Graduate School of Medicine Kyoto University Kyoto Japan
| | - Kentaro Watanabe
- Department of Pediatrics, Graduate School of Medicine The University of Tokyo Tokyo Japan
| | - Mitsuteru Hiwatari
- Department of Pediatrics, Graduate School of Medicine The University of Tokyo Tokyo Japan
| | - Satoru Miyano
- Laboratory of DNA Information Analysis, Human Genome Center, Institute of Medical Science The University of Tokyo Tokyo Japan
| | - Seishi Ogawa
- Department of Pathology and Tumor Biology, Graduate School of Medicine Kyoto University Kyoto Japan
| | - Junko Takita
- Department of Pediatrics, Graduate School of Medicine The University of Tokyo Tokyo Japan
- Department of Pediatrics, Graduate School of Medicine Kyoto University Kyoto Japan
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22
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Role of Cyclin D1 and BCOR Immunohistochemistry in Differentiating Clear Cell Sarcoma of Kidney From its Mimics. J Pediatr Hematol Oncol 2021; 43:294-300. [PMID: 34673711 DOI: 10.1097/mph.0000000000002262] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Accepted: 06/21/2021] [Indexed: 01/14/2023]
Abstract
BACKGROUND AND AIM Clear cell sarcoma of kidney (CCSK) is the second most common pediatric renal malignancy, constituting ∼3% of renal tumors. Due to its morphologic diversity, the diagnosis of CCSK is often challenging. Recent studies have identified internal tandem duplication of BCL6 corepressor (BCOR) gene in CCSKs which coupled with cyclin D1 immunoreactivity, is helpful in differentiating it from its mimics, particularly blastema-rich Wilms tumor (WT), malignant rhabdoid tumor (MRT), and congenital mesoblastic nephroma (CMN). We aimed to evaluate the utility of cyclin D1 and BCOR immunohistochemistry in differentiating CCSK from its morphologic mimics. MATERIALS AND METHODS Our cohort comprised of 38 pediatric renal tumors which included CCSK (n=18), WT (n=10), MRT (n=5), and CMN (n=5) cases. A detailed clinicopathologic analysis was performed, and tissue microarray were constructed for CCSK and WT, while MRT and CMN tumors were individually stained. RESULTS The age ranged from 2 months to 16 years with male:female ratio of 3:1. Strong, diffuse nuclear immunoreactivity for cyclin D1 and BCOR was noted in 61% (n=11/18) and 83% (n=15/18) of CCSK, respectively, while it was significantly less in WT (n=3/10 for cyclin D1) (n=2/10 for BCOR). None of the MRT and CMN examples demonstrated any immunoreactivity. Interestingly, only the blastemal component of WTs showed distinct, rare nuclear immunoreactivity for cyclin D1 or BCOR and the combination of these was never positive in a given case. CONCLUSION Our results provide evidence that concurrent immunopositivity with cyclin D1 and BCOR is helpful in distinguishing CCSK from its morphologic mimics.
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23
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Friesenbichler W, Lüftinger R, Kropshofer G, Henkel M, Amann G, Furtwängler R, Graf N, Kager L. Clear cell sarcoma of the kidney in Austrian children: Long-term survival after relapse. Pediatr Blood Cancer 2021; 68:e28860. [PMID: 33438324 DOI: 10.1002/pbc.28860] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2020] [Revised: 11/21/2020] [Accepted: 12/05/2020] [Indexed: 11/06/2022]
Abstract
INTRODUCTION Clear cell sarcoma of the kidney (CCSK) is a rare malignant childhood renal tumour. Recently, the central nervous system (CNS) was found to be the most frequent site of relapse associated with a poor outcome. Optimal treatment strategies are scarce. PATIENTS AND METHODS Retrospective data analysis of all Austrian children with CCSK. They were enrolled in the Austrian-Hungarian Wilms Tumour Study (AHWTS) 1989, the SIOP93-01 or the SIOP2001 study between 1990 and 2019. Demographic, diagnostic, treatment-related variables and survival data were analysed. RESULTS We identified 12 children with CCSK (M = 7, F = 5; median age 1.6 years). All had localised disease (stage I: 2; stage II: 2; stage III: 8) at diagnosis, and a first complete remission (CR1) was achieved in 12/12. Six patients are in an ongoing CR1 (median follow-up 10 years). Six other patients had a relapse (local 1; brain 5) a median time of 2.4 years from diagnosis. Two patients died of the disease 4 months and 2.8 years after first relapse. Four of five patients with CNS relapse are in CR2 with a median follow-up time of 9.3 years after relapse diagnosis. Relapse treatment included a combination of chemotherapy, radiation and surgery. Two children received high-dose chemotherapy followed by autologous stem cell rescue, and one child received intrathecal mafosphamide. Long-term side effects after treatment were impaired tubular renal function (n = 4), cardiomyopathy (n = 1) and growth disorders (n = 1). CONCLUSIONS In this series, the brain was the most common site of relapse. Long-term survival after recurrence was achievable with intensive multimodal therapy.
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Affiliation(s)
- Waltraud Friesenbichler
- Department of Paediatric Haematology and Oncology, St. Anna Children's Hospital, Medical University, Vienna, Austria
| | - Roswitha Lüftinger
- Department of Paediatric Haematology and Oncology, St. Anna Children's Hospital, Medical University, Vienna, Austria
| | - Gabriele Kropshofer
- Department of Paediatrics, University Hospital Innsbruck, Innsbruck, Austria
| | - Martin Henkel
- Department of Paediatrics, Hospital of Barmherzige Schwestern Linz, Linz, Austria
| | - Gabriele Amann
- Institute of Pathology, Medical University of Vienna, Vienna, Austria
| | - Rhoikos Furtwängler
- Department of Paediatrics, University Hospital Homburg/Saar, Homburg, Germany
| | - Norbert Graf
- Department of Paediatrics, University Hospital Homburg/Saar, Homburg, Germany
| | - Leo Kager
- Department of Paediatric Haematology and Oncology, St. Anna Children's Hospital, Medical University, Vienna, Austria.,Children's Cancer Research Institute, Vienna, Austria
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24
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Kang C, Shin HJ, Yoon H, Han JW, Lyu CJ, Lee MJ. Differentiation between Clear Cell Sarcoma of the Kidney and Wilms' Tumor with CT. Korean J Radiol 2021; 22:1185-1193. [PMID: 33856131 PMCID: PMC8236369 DOI: 10.3348/kjr.2020.0882] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Revised: 10/09/2020] [Accepted: 10/13/2020] [Indexed: 01/18/2023] Open
Abstract
Objective Clear cell sarcoma of the kidney (CCSK) is the second-most common but extremely rare primary renal malignancy in children after Wilms' tumor. The aims of this study were to evaluate the imaging features that could distinguish between CCSK and Wilms' tumor and to assess the features with diagnostic value for identifying CCSK. Materials and Methods We reviewed the initial contrast-enhanced abdominal-pelvic CT scans of children with CCSK and Wilms' tumor between 2010 to 2019. Fifty-eight children (32 males and 26 females; age, 0.3–10 years), 7 with CCSK, and 51 with Wilms' tumor, were included. The maximum tumor diameter, presence of engorged perinephric vessels, maximum density of the tumor (Tmax) of the enhancing solid portion, paraspinal muscle, contralateral renal vein density, and density ratios (Tmax/muscle and Tmax/vein) were analyzed on the renal parenchymal phase of contrast-enhanced CT. Fisher's exact tests and Mann-Whitney U tests were conducted to analyze the categorical and continuous variables, respectively. Logistic regression and receiver operating characteristic curve analyses were also performed. Results The age, sex, and tumor diameter did not differ between the two groups. Engorged perinephric vessels were more common in patients in the CCSK group (71% [5/7] vs. 16% [8/51], p = 0.005). Tmax (median, 148.0 vs. 111.0 Hounsfield unit, p = 0.004), Tmax/muscle (median, 2.64 vs. 1.67, p = 0.002), and Tmax/vein (median, 0.94 vs. 0.59, p = 0.002) were higher in the CCSK compared to the Wilms' group. Multiple logistic regression revealed that engorged vessels (odds ratio 13.615; 95% confidence interval [CI], 1.770–104.730) and Tmax/muscle (odds ratio 5.881; 95% CI, 1.337–25.871) were significant predictors of CCSK. The cutoff values of Tmax/muscle (86% sensitivity, 77% specificity) and Tmax/vein (71% sensitivity, 86% specificity) for the diagnosis of CCSK were 1.97 and 0.76, respectively. Conclusion Perinephric vessel engorgement and greater tumor enhancement (Tmax/muscle > 1.97 or Tmax/vein > 0.76) are helpful for differentiating between CCSK and Wilms' tumor in children aged below 10 years.
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Affiliation(s)
- Choeum Kang
- Department of Radiology and Research Institute of Radiological Science, Severance Children's Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Hyun Joo Shin
- Department of Radiology and Research Institute of Radiological Science, Severance Children's Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Haesung Yoon
- Department of Radiology and Research Institute of Radiological Science, Severance Children's Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jung Woo Han
- Division of Pediatric Hematology and Oncology, Department of Pediatrics, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Chuhl Joo Lyu
- Division of Pediatric Hematology and Oncology, Department of Pediatrics, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Mi Jung Lee
- Department of Radiology and Research Institute of Radiological Science, Severance Children's Hospital, Yonsei University College of Medicine, Seoul, Korea.
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25
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Dong JJ, He XY, Liu X, Lin T, He DW, Liu F, Wei GH. Retrospective analysis of outcomes in patients with clear cell sarcoma of the kidney: A tertiary single-institution experience. J Pediatr Surg 2021; 56:580-586. [PMID: 33272561 DOI: 10.1016/j.jpedsurg.2020.07.022] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Revised: 07/15/2020] [Accepted: 07/17/2020] [Indexed: 10/23/2022]
Abstract
BACKGROUND Clear cell sarcoma of the kidney (CCSK) is a rare and aggressive tumor. This study aims to describe the clinical characteristics and outcomes of CCSK patients in one of the largest pediatric medical centers in China. METHODS We included all patients diagnosed with CCSK between January 2008 and March 2019 at the Children's Hospital of Chongqing Medical University, China. The patients' demographics, clinical presentation, and management were reviewed. Follow-up was continued until December 2019. RESULTS In total, 41 CCSK patients (66% male) with a median age of 24 months (range 3-108 months) were identified. The stage distributions of stages I, II, III and IV were 42%, 34%, 24% and 0%, respectively. Preoperative chemotherapy was administered to 7/41 patients. All patients underwent radical nephrectomy and postoperative chemotherapy. The median number of lymph nodes sampled was 4 (range 1-12). Radiotherapy was applied in 8/41 patients. The 5-year event-free survival (EFS) and overall survival (OS) were 63.9% and 78.8%, respectively. Of the 41 patients, 11 patients experienced relapse at a median time of 19 months (range 5-72 months). The most common site of recurrence was the tumor bed (9/11). Young age was a significant adverse prognostic factor for EFS. CONCLUSIONS The overall outcome of CCSK patients in our hospital is poorer than that in developed regions. More research is needed to clarify the underlying causes of poorer outcomes in young patients and improve outcomes. TYPE OF STUDY Retrospective study. LEVEL OF EVIDENCE LEVEL IV.
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Affiliation(s)
- Jun-Jun Dong
- Department of Urology, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, 136 Zhongshan 2nd RD, Yuzhong District, Chongqing 400014, China
| | - Xing-Yue He
- Department of Urology, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, 136 Zhongshan 2nd RD, Yuzhong District, Chongqing 400014, China
| | - Xing Liu
- Department of Urology, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, 136 Zhongshan 2nd RD, Yuzhong District, Chongqing 400014, China
| | - Tao Lin
- Department of Urology, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, 136 Zhongshan 2nd RD, Yuzhong District, Chongqing 400014, China
| | - Da-Wei He
- Department of Urology, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, 136 Zhongshan 2nd RD, Yuzhong District, Chongqing 400014, China
| | - Feng Liu
- Department of Urology, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, 136 Zhongshan 2nd RD, Yuzhong District, Chongqing 400014, China.
| | - Guang-Hui Wei
- Department of Urology, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, 136 Zhongshan 2nd RD, Yuzhong District, Chongqing 400014, China; Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing Key Laboratory of Pediatric, 136 Zhongshan 2nd RD, Yuzhong District, Chongqing 400014, China.
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26
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Abstract
Renal tumors are rare in the neonatal period. Although some may be detected prenatally, a greater proportion present after birth, most often with a palpable abdominal mass with or without other associated symptoms. Cross-sectional imaging is typically followed by radical nephrectomy to make a specific histologic diagnosis to determine the need for additional therapy. This article reviews the clinical presentation, workup, treatment, and outcomes for neonates with some of the more common renal tumors seen in this population.
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Affiliation(s)
- Sei-Gyung K Sze
- Maine Children's Cancer Program, Department of Pediatrics, Maine Medical Center, Tufts School of Medicine, 100 Campus Drive, Suite 107, Scarborough, ME 04074, USA.
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27
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Gao H, Cheng QY, Zhao Q, Tao LX, Zhang C. Childhood Clear Cell Sarcoma of Kidney: Incidence and Survival. Front Pediatr 2021; 9:675373. [PMID: 34095035 PMCID: PMC8173214 DOI: 10.3389/fped.2021.675373] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Accepted: 04/21/2021] [Indexed: 12/26/2022] Open
Abstract
This study is to describe current incidence of childhood clear cell sarcoma of kidney (CCSK) and to investigate the present survival of this cancer. Surveillance, Epidemiology, and End Result (SEER) data was used to identify children with CCSK and Wilms tumor (WT) aged 0-19 years in the US. Age-adjusted incidences were estimated over the decades. Age- and sex-specific epidemiology was also presented. Propensity score matching was used to balance features of CCSK and WT cases. Log rank test was used to compare survivals and Cox regression was used to evaluate independent effects of factors. The present age-adjusted incidence of childhood CCSK was 0.205 per million, which remained stable for years and ranked third in all pediatric renal tumors. The incidence rate ratios for boy and age under 4 were 3 and 21, respectively. The current 5-year overall survival (OS) rate for CCSK was 87%, which is not evidently inferior to that for WT (90%); however the outcome of CCSK was significantly poorer if both groups were well-balanced (OS rate was 86 vs. 95%). Early year of diagnosis and distant metastasis were independent survival factors. In conclusion, occurrence of CCSK remains stable over the years, with an age-adjusted incidence of 0.205 per million. Boy and age under 4 are risk factors for tumor development. CCSK currently has a favorable outcome but its nature may be more aggressive than common kidney tumor, which in turn proves efficacy of modern treatment.
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Affiliation(s)
- Hui Gao
- Department of Pediatrics, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Qi-Yuan Cheng
- Department of Pediatrics, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Qian Zhao
- Department of Pediatrics, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Long-Xiang Tao
- Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Cheng Zhang
- Anhui Provincial Cancer Institute, The First Affiliated Hospital of Anhui Medical University, Hefei, China
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28
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Birkemeier KL. Imaging of solid congenital abdominal masses: a review of the literature and practical approach to image interpretation. Pediatr Radiol 2020; 50:1907-1920. [PMID: 33252758 DOI: 10.1007/s00247-020-04678-1] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Revised: 02/27/2020] [Accepted: 04/13/2020] [Indexed: 12/12/2022]
Abstract
Fetal abdominal tumors are rare, usually benign, and cause a great deal of anxiety for expectant parents and the physicians counseling them. In this paper the author reviews the most common fetal abdominal tumors in the liver (hemangioma, mesenchymal hamartoma, hepatoblastoma, metastases) and the kidney (congenital mesoblastic nephroma, Wilms tumor, malignant rhabdoid tumor, and clear cell sarcoma), and suprarenal mass lesions (adrenal neuroblastoma, adrenal hemorrhage, and subdiaphragmatic extralobar pulmonary sequestration). The author describes the imaging approach, imaging appearance and differentiating features of tumors, and differences between fetal and childhood appearances of tumors.
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Affiliation(s)
- Krista L Birkemeier
- Department of Radiology, Pediatric Section, Baylor Scott and White Health-Temple, McLane Children's Medical Center, Texas A&M Health Science Center, 2401 S. 31st St., MS-01-W256, Temple, TX, 76508, USA.
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29
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Qureshi SS, Bhagat M, Verma K, Yadav S, Prasad M, Vora T, Chinnaswamy G, Amin N, Smriti V, Baheti A, Laskar S, Khanna N, Ramadwar M, Shah S. Incidence, treatment, and outcomes of primary and recurrent Non-Wilms renal tumors in children: Report of 109 patients treated at a single institution. J Pediatr Urol 2020; 16:475.e1-475.e9. [PMID: 32620510 DOI: 10.1016/j.jpurol.2020.05.168] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Revised: 05/22/2020] [Accepted: 05/28/2020] [Indexed: 12/17/2022]
Abstract
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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Affiliation(s)
- Sajid S Qureshi
- Division of Paediatric Surgical Oncology, Department of Surgical Oncology, Tata Memorial Hospital and Advanced Centre for Training Research and Education in Cancer (ACTREC), Tata Memorial Centre, Mumbai, India; Homi Bhabha National Institute (HBNI), Mumbai, India.
| | - Monica Bhagat
- Division of Paediatric Surgical Oncology, Department of Surgical Oncology, Tata Memorial Hospital and Advanced Centre for Training Research and Education in Cancer (ACTREC), Tata Memorial Centre, Mumbai, India
| | - Kamlesh Verma
- Division of Paediatric Surgical Oncology, Department of Surgical Oncology, Tata Memorial Hospital and Advanced Centre for Training Research and Education in Cancer (ACTREC), Tata Memorial Centre, Mumbai, India
| | - Subhash Yadav
- Homi Bhabha National Institute (HBNI), Mumbai, India; Department of Pathology, Tata Memorial Hospital and Advanced Centre for Training Research and Education in Cancer (ACTREC), Tata Memorial Centre, Mumbai, India
| | - Maya Prasad
- Homi Bhabha National Institute (HBNI), Mumbai, India; Division of Pediatric Oncology, Department of Medical Oncology, Tata Memorial Hospital and Advanced Centre for Training Research and Education in Cancer (ACTREC), Tata Memorial Centre, Mumbai, India
| | - Tushar Vora
- Homi Bhabha National Institute (HBNI), Mumbai, India; Division of Pediatric Oncology, Department of Medical Oncology, Tata Memorial Hospital and Advanced Centre for Training Research and Education in Cancer (ACTREC), Tata Memorial Centre, Mumbai, India
| | - Girish Chinnaswamy
- Homi Bhabha National Institute (HBNI), Mumbai, India; Division of Pediatric Oncology, Department of Medical Oncology, Tata Memorial Hospital and Advanced Centre for Training Research and Education in Cancer (ACTREC), Tata Memorial Centre, Mumbai, India
| | - Nayana Amin
- Homi Bhabha National Institute (HBNI), Mumbai, India; Department of Anesthesia, Tata Memorial Hospital, Tata Memorial Hospital and Advanced Centre for Training Research and Education in Cancer (ACTREC), Tata Memorial Centre, Mumbai, India
| | - Vasundhara Smriti
- Homi Bhabha National Institute (HBNI), Mumbai, India; Department of Radiology, Tata Memorial Hospital, Tata Memorial Hospital and Advanced Centre for Training Research and Education in Cancer (ACTREC), Tata Memorial Centre, Mumbai, India
| | - Akshay Baheti
- Homi Bhabha National Institute (HBNI), Mumbai, India; Department of Radiology, Tata Memorial Hospital, Tata Memorial Hospital and Advanced Centre for Training Research and Education in Cancer (ACTREC), Tata Memorial Centre, Mumbai, India
| | - Siddharth Laskar
- Homi Bhabha National Institute (HBNI), Mumbai, India; Department of Radiation Oncology, Tata Memorial Hospital and Advanced Centre for Training Research and Education in Cancer (ACTREC), Tata Memorial Centre, Mumbai, India
| | - Nehal Khanna
- Homi Bhabha National Institute (HBNI), Mumbai, India; Department of Radiation Oncology, Tata Memorial Hospital and Advanced Centre for Training Research and Education in Cancer (ACTREC), Tata Memorial Centre, Mumbai, India
| | - Mukta Ramadwar
- Homi Bhabha National Institute (HBNI), Mumbai, India; Department of Pathology, Tata Memorial Hospital and Advanced Centre for Training Research and Education in Cancer (ACTREC), Tata Memorial Centre, Mumbai, India
| | - Sneha Shah
- Homi Bhabha National Institute (HBNI), Mumbai, India; Department of Nuclear Medicine, Tata Memorial Centre, Bombay, India
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30
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Jones BC, Youlden DR, Cundy TP, O'Callaghan ME, Karpelowsky J, Aitken JF, McBride CA. Renal tumours in Australian children: 30 years of incidence, outcome and second primary malignancy data from the Australian Childhood Cancer Registry. J Paediatr Child Health 2020; 56:908-916. [PMID: 31943452 DOI: 10.1111/jpc.14774] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2019] [Revised: 12/01/2019] [Accepted: 12/12/2019] [Indexed: 11/30/2022]
Abstract
AIM This paper describes the incidence and outcomes of childhood renal malignancies in Australia using national population-based data from the Australian Childhood Cancer Registry. METHODS De-identified data for children (0-14 years) diagnosed with renal malignancies from 1983 to 2015 inclusive were extracted. Cause-specific (CSS) and event-free survival up to 20 years from diagnosis were estimated using the cohort method. Adjusted excess mortality hazard ratios were calculated using a multivariable flexible parametric survival model. Details relating to second primary malignancies (SPMs) were also examined. RESULTS There were 1046 children diagnosed with renal malignancies in Australia between 1983 and 2015 (91% nephroblastoma), generating an annual age-standardised incidence rate of 8 per million children, which remained constant over the study period. CSS was 89% (95% confidence interval = 87-91%) and 88% (86-90%) at 5 and 20 years, respectively, and 5-year event-free survival was 82% (80-84%). Five-year CSS did not change over the study period and was highest for nephroblastoma (91%). Of the 94% of patients achieving remission, 15% relapsed and subsequent 5-year CSS was 49% (40%-58%). Eleven children were diagnosed with SPM (standardised incidence ratio = 2.9, 95% confidence interval = 1.6-5.3, P < 0.001), and five of them (45%) died within 5 years of the second diagnosis. CONCLUSIONS Children treated for renal malignancies in Australia have excellent long-term survival, which is unchanged since 1983. SPMs are uncommon following treatment for childhood renal cancer but carry a poor prognosis. Relapse carries a similarly poor prognosis to SPM but is more common. These data are comparable to registry outcomes in similarly developed nations.
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Affiliation(s)
- Brendan C Jones
- Department of Paediatric Surgery, Children's Health Queensland Hospital and Health Service, Queensland Children's Hospital, Brisbane, Queensland, Australia.,Discipline of Paediatrics and Child Health, University of Queensland, Brisbane, Queensland, Australia
| | - Danny R Youlden
- Australian Childhood Cancer Registry, Cancer Council Queensland, Brisbane, Queensland, Australia.,Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia
| | - Thomas P Cundy
- Department of Paediatric Surgery, Women's and Children's Hospital, Adelaide, South Australia, Australia.,Discipline of Surgery, University of Adelaide, Adelaide, South Australia, Australia
| | - Michael E O'Callaghan
- Department of Urology, Flinders Medical Centre, Adelaide, South Australia, Australia.,Flinders Centre for Innovation in Cancer, Flinders University, Adelaide, South Australia, Australia.,Discipline of Medicine, University of Adelaide, Adelaide, South Australia, Australia
| | - Jonathan Karpelowsky
- Department of Paediatric Surgery, The Children's Hospital, Westmead, New South Wales, Australia.,Division of Child and Adolescent Health, University of Sydney, Westmead, New South Wales, Australia.,Children's Cancer Research Unit, Kids Research Institute, Westmead, New South Wales, Australia
| | - Joanne F Aitken
- Australian Childhood Cancer Registry, Cancer Council Queensland, Brisbane, Queensland, Australia.,Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia.,School of Public Health, University of Queensland, Brisbane, Queensland, Australia.,Institute for Resilient Regions, University of Southern Queensland, Brisbane, Queensland, Australia
| | - Craig A McBride
- Department of Paediatric Surgery, Children's Health Queensland Hospital and Health Service, Queensland Children's Hospital, Brisbane, Queensland, Australia.,Discipline of Paediatrics and Child Health, University of Queensland, Brisbane, Queensland, Australia.,Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland, Australia
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31
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Melchior P, Dzierma Y, Rübe C, Graf N, Kager L, Dieckmann K, Kroiss S, Hubertus J, Warmann S, Schenk JP, Leuschner I, Nemes K, Meier CM, Vokuhl C, Frühwald M, Furtwängler R. Local Stage Dependent Necessity of Radiation Therapy in Rhabdoid Tumors of the Kidney (RTK). Int J Radiat Oncol Biol Phys 2020; 108:667-675. [PMID: 32407933 DOI: 10.1016/j.ijrobp.2020.04.046] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2019] [Revised: 03/15/2020] [Accepted: 04/30/2020] [Indexed: 12/22/2022]
Abstract
PURPOSE Rhabdoid tumor of the kidney (RTK) is one of the most aggressive childhood renal tumors. Overall survival ranges from 22% to 47%. The indication for radiation therapy (RT) in usually very young patients is an ongoing discussion. Recent protocols recommend RT independent of local stage, the latter being a good discriminator in other childhood kidney tumors. In this study, we analyze the evidence for RT in regard to risk factors, including tumor stage. METHODS AND MATERIALS This study analyzed 58 patients with RTK from Austria, Switzerland, and Germany treated in the framework of 4 consecutive, prospective renal/rhabdoid tumor studies from 1991 to 2014. All treatment protocols included multimodality treatment, including high-intensity chemotherapy, surgery, and RT. RESULTS Local stage distribution was not applicable, I, II, and III in 1, 6, 11, and 40, respectively. Twenty-nine (50%) patients had stage IV disease at diagnosis. Thirty-seven patients (64%) achieved complete remission, and 49% (18/37) relapsed. Thirty-four patients (60%) patients had progressive disease and died, 17 had local disease, 10 had combined disease, and 7 had distant disease; 2 treatment-related deaths were reported (3%). Twenty-one patients received RT during first-line treatment, 18 of them to all involved sites. Eight of the 34 cases of progressive disease occurred in irradiated patients. The local failure rate of treated patients with local stage II or III disease was 29% (6/18) in patients irradiated to all sites compared with 68% (15/22) in nonirradiated patients. One of 6 stage I patients received RT, and 1 patient experienced distant relapse (2-year progression-free and overall survival both 83% ± 15%). Progression-free survival for local stage II and III disease treated with RT, adjusted for early relapse or treatment abandonment, was 67% ± 11%, compared with 15% ± 7% without RT (P < .0001). CONCLUSION The 68% local failure rate in nonirradiated patients underlines the importance of local treatment. Our experience supports the use of RT for local control in higher stage disease. In contrast, no local relapse in 6 local stage I patients, including 5 nonirradiated patients, suggests omission of RT in this favorable subset of usually infant patients with RTK.
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Affiliation(s)
- Patrick Melchior
- Department of Radiation Oncology, Saarland University Hospital, Homburg, Germany.
| | - Yvonne Dzierma
- Department of Radiation Oncology, Saarland University Hospital, Homburg, Germany
| | - Christian Rübe
- Department of Radiation Oncology, Saarland University Hospital, Homburg, Germany
| | - Norbert Graf
- Department of Pediatric Hematology and Oncology, Saarland University Hospital, Homburg/Saar, Germany
| | - Leo Kager
- St. Anna Children's Hospital, Department of Pediatrics, Medical University Vienna, Vienna, Austria
| | - Karin Dieckmann
- Department of Radiation Oncology, Medical University Vienna, Vienna, Austria
| | - Sabine Kroiss
- Department of Pediatric Hematology and Oncology, Children's Hospital, Zurich University, Zurich, Switzerland
| | - Jochen Hubertus
- Department of Pediatric Surgery, von Haunersches Kinderspital, Ludwigs-Maximilians University, Munich, Germany
| | - Steven Warmann
- Department of Pediatric Surgery, Tübingen University Hospital, Tübingen, Germany
| | - Jens-Peter Schenk
- Department of Radiology, Heidelberg University Hospital, Heidelberg, Germany
| | - Ivo Leuschner
- Department of Paidopathology, Schleswig-Holstein-University Hospital, Campus Kiel, Kiel, Germany; Section of Pediatric Pathology, Department of Pathology, University Hospital Bonn, Bonn, Germany
| | - Karolina Nemes
- Swabian Children's Cancer Center, University Children's Hospital Augsburg, Augsburg, Germany
| | | | - Christian Vokuhl
- Department of Paidopathology, Schleswig-Holstein-University Hospital, Campus Kiel, Kiel, Germany; Deceased
| | - Michael Frühwald
- Swabian Children's Cancer Center, University Children's Hospital Augsburg, Augsburg, Germany
| | - Rhoikos Furtwängler
- Department of Pediatric Hematology and Oncology, Saarland University Hospital, Homburg/Saar, Germany
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32
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Han H, Bertrand KC, Patel KR, Fisher KE, Roy A, Muscal JA, Venkatramani R. BCOR-CCNB3 fusion-positive clear cell sarcoma of the kidney. Pediatr Blood Cancer 2020; 67:e28151. [PMID: 31876361 DOI: 10.1002/pbc.28151] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Revised: 12/10/2019] [Accepted: 12/11/2019] [Indexed: 11/08/2022]
Abstract
Clear cell sarcoma of the kidney (CCSK) is the second most common malignant pediatric renal tumor. Two of the recurrent somatic alterations reported in CCSK are BCL-6 corepressor (BCOR) internal tandem duplication (ITD) and YWHAE-NUTM2B/E gene fusion. A minority of patients with CCSKs have other rare somatic alterations. We report two patients with CCSK showing BCOR-CCNB3 (where CCNB3 is cyclin B3) fusion, who had similar clinical presentation of a large renal mass with tumor thrombus extending through the inferior vena cava into the right atrium and a favorable response to chemotherapy. We recommend BCOR-CCNB3 fusion testing for all patients with CCSK who lack BCOR-ITD or YWHAE-NUTM2B/E gene fusions.
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Affiliation(s)
- Hyojeong Han
- Section of Hematology/Oncology, Department of Pediatrics, Texas Children's Hospital/Baylor College of Medicine, Houston, Texas
| | - Kelsey C Bertrand
- Section of Hematology/Oncology, Department of Pediatrics, Texas Children's Hospital/Baylor College of Medicine, Houston, Texas
| | - Kalyani R Patel
- Department of Pathology & Immunology, Texas Children's Hospital/Baylor College of Medicine, Houston, Texas
| | - Kevin E Fisher
- Department of Pathology & Immunology, Texas Children's Hospital/Baylor College of Medicine, Houston, Texas
| | - Angshumoy Roy
- Section of Hematology/Oncology, Department of Pediatrics, Texas Children's Hospital/Baylor College of Medicine, Houston, Texas.,Department of Pathology & Immunology, Texas Children's Hospital/Baylor College of Medicine, Houston, Texas
| | - Jodi A Muscal
- Section of Hematology/Oncology, Department of Pediatrics, Texas Children's Hospital/Baylor College of Medicine, Houston, Texas
| | - Rajkumar Venkatramani
- Section of Hematology/Oncology, Department of Pediatrics, Texas Children's Hospital/Baylor College of Medicine, Houston, Texas
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33
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Wang Z, Virgolin M, Bosman PAN, Crama KF, Balgobind BV, Bel A, Alderliesten T. Automatic generation of three-dimensional dose reconstruction data for two-dimensional radiotherapy plans for historically treated patients. J Med Imaging (Bellingham) 2020; 7:015001. [PMID: 32042857 DOI: 10.1117/1.jmi.7.1.015001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2019] [Accepted: 01/17/2020] [Indexed: 01/10/2023] Open
Abstract
Performing large-scale three-dimensional radiation dose reconstruction for patients requires a large amount of manual work. We present an image processing-based pipeline to automatically reconstruct radiation dose. The pipeline was designed for childhood cancer survivors that received abdominal radiotherapy with anterior-to-posterior and posterior-to-anterior field set-up. First, anatomical landmarks are automatically identified on two-dimensional radiographs. Second, these landmarks are used to derive parameters to emulate the geometry of the plan on a surrogate computed tomography. Finally, the plan is emulated and used as input for dose calculation. For qualitative evaluation, 100 cases of automatic and manual plan emulations were assessed by two experienced radiation dosimetrists in a blinded comparison. The two radiation dosimetrists approved 100%/100% and 92%/91% of the automatic/manual plan emulations, respectively. Similar approval rates of 100% and 94% hold when the automatic pipeline is applied on another 50 cases. Further, quantitative comparisons resulted in on average < 5 mm difference in plan isocenter/borders, and < 0.9 Gy in organ mean dose (prescribed dose: 14.4 Gy) calculated from the automatic and manual plan emulations. No statistically significant difference in terms of dose reconstruction accuracy was found for most organs at risk. Ultimately, our automatic pipeline results are of sufficient quality to enable effortless scaling of dose reconstruction data generation.
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Affiliation(s)
- Ziyuan Wang
- University of Amsterdam, Amsterdam UMC, Department of Radiation Oncology, Amsterdam, The Netherlands
| | - Marco Virgolin
- Centrum Wiskunde and Informatica, Life Sciences and Health Group, Amsterdam, The Netherlands
| | - Peter A N Bosman
- Centrum Wiskunde and Informatica, Life Sciences and Health Group, Amsterdam, The Netherlands
| | - Koen F Crama
- University of Amsterdam, Amsterdam UMC, Department of Radiation Oncology, Amsterdam, The Netherlands
| | - Brian V Balgobind
- University of Amsterdam, Amsterdam UMC, Department of Radiation Oncology, Amsterdam, The Netherlands
| | - Arjan Bel
- University of Amsterdam, Amsterdam UMC, Department of Radiation Oncology, Amsterdam, The Netherlands
| | - Tanja Alderliesten
- University of Amsterdam, Amsterdam UMC, Department of Radiation Oncology, Amsterdam, The Netherlands
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34
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Khan MZ, Akhtar N, Hassan U, Mushtaq S. Diagnostic Utility of BCOR Antibody in Clear Cell Sarcomas of Kidney. Int J Surg Pathol 2019; 28:477-481. [DOI: 10.1177/1066896919895119] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
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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Affiliation(s)
| | - Noreen Akhtar
- Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan
| | - Usman Hassan
- Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan
| | - Sajid Mushtaq
- Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan
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35
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36
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Abstract
Pediatric and adolescent renal tumors account for approximately 7% of all new cancer diagnoses in the USA each year. The prognosis and treatment are varied based on factors including the underlying histology and tumor stage, with survival rates ranging from greater than 90% in favorable histology Wilms tumor to almost universally fatal in other disease types, including those patients with advanced stage malignant rhabdoid tumor and renal medullary carcinoma. In recent years, our understanding of the underlying genetic drivers of the different types of pediatric kidney cancer has dramatically increased, opening the door to utilization of new targeted biologic agents alone or in combination with conventional chemotherapy to improve outcomes. Several ongoing clinical trials are investigating the use of a variety of targeted agents in pediatric patients with underlying genetic aberrations. In this manuscript, the underlying biology and early phase clinical trials relevant to pediatric renal cancers are reviewed.
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Affiliation(s)
- Amy L Walz
- Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
| | | | - James I Geller
- Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
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37
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Gros SJ, Holland-Cunz SG, Supuran CT, Braissant O. Personalized Treatment Response Assessment for Rare Childhood Tumors Using Microcalorimetry-Exemplified by Use of Carbonic Anhydrase IX and Aquaporin 1 Inhibitors. Int J Mol Sci 2019; 20:ijms20204984. [PMID: 31600976 PMCID: PMC6834116 DOI: 10.3390/ijms20204984] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Revised: 10/03/2019] [Accepted: 10/05/2019] [Indexed: 12/19/2022] Open
Abstract
We present a novel approach to a personalized therapeutic concept for solid tumors. We illustrate this on a rare childhood tumor for which only a generalized treatment concept exists using carbonic anhydrase IX and aquaporin 1 inhibitors. The use of microcalorimetry as a refined in vitro method for evaluation of drug susceptibility in organotypic slice culture has not previously been established. Rapid microcalorimetric drug response assessment can refine a general treatment concept when it is applied in cases in which tumors do not respond to conventional chemo-radiation treatment. For solid tumors, which do not respond to classical treatment, and especially for rare tumors without an established protocol rapid microcalorimetric drug response testing presents an elegant novel approach to test alternative therapeutic approaches. While improved treatment concepts have led to improved outcome over the past decades, the prognosis of high risk disease is still poor and rethinking of clinical trial design is necessary. A small patient population combined with the necessity to assess experimental therapies for rare solid tumors rather at the time of diagnosis than in relapsed or refractory patients provides great challenges. The possibility to rapidly compare established protocols with innovative therapeutics presents an elegant novel approach to refine and personalize treatment.
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Affiliation(s)
- Stephanie J Gros
- Department of Pediatric Surgery, University Children's Hospital Basel, 4031 Basel, Switzerland.
| | - Stefan G Holland-Cunz
- Department of Pediatric Surgery, University Children's Hospital Basel, 4031 Basel, Switzerland.
| | - Claudiu T Supuran
- Department Neurofarba, Sezione di Scienze farmaceutiche, University of Florence, 50139 Florence, Italy.
| | - Olivier Braissant
- Biological Calorimetry Lab, Department of Biomedical Engineering, University of Basel, 4123 Allschwil, Basel, Switzerland.
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Stanescu AL, Acharya PT, Lee EY, Phillips GS. Pediatric Renal Neoplasms:: MR Imaging-Based Practical Diagnostic Approach. Magn Reson Imaging Clin N Am 2019; 27:279-290. [PMID: 30910098 DOI: 10.1016/j.mric.2019.01.006] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Pediatric renal tumors may be malignant or benign. Wilms tumor, the most common malignant pediatric renal tumor, arises sporadically or with various syndromes. Renal cell carcinoma typically presents in older children. Renal clear cell sarcoma and rhabdoid tumor are typically less common, more aggressive, and present in younger children. Benign renal tumors include mesoblastic nephroma, multilocular cystic renal tumor, angiomyolipoma, and metanephric adenoma. Lymphoma and leukemia may secondarily involve the kidney. Although there is overlap in the imaging appearance of several pediatric renal tumors, magnetic resonance characteristics and clinical data narrow the differential diagnosis and suggest a specific diagnosis. This article reviews current MR techniques, as well as the common MR imaging characteristics of malignant and benign pediatric renal neoplasms.
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Affiliation(s)
- A Luana Stanescu
- Department of Radiology, Seattle Children's, University of Washington, 4800 Sand Point Way Northeast, Seattle, WA 98105, USA.
| | - Patricia T Acharya
- Department of Radiology, Loma Linda University Children's Hospital, 11234 Anderson Street, Room 2835, Loma Linda, CA 92354, USA
| | - Edward Y Lee
- Division of Thoracic Imaging, Department of Radiology, Boston Children's Hospital, Harvard Medical School, 330 Longwood Avenue, Boston, MA 02115, USA
| | - Grace S Phillips
- Department of Radiology, Seattle Children's, University of Washington, 4800 Sand Point Way Northeast, Seattle, WA 98105, USA
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Vokuhl C. [Rare childhood kidney tumors]. DER PATHOLOGE 2019; 40:600-608. [PMID: 31338565 DOI: 10.1007/s00292-019-0638-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Pediatric kidney tumors are rare and account for about 6% of all childhood malignancies. By far the most common tumors are nephroblastomas. This review presents rare childhood renal tumors. Mesoblastic nephroma, as tumors of the low risk group, as well as the clear-cell sarcomas of the kidney and malignant rhabdoid tumors, as tumors of the high-risk group, and the so-called anaplastic sarcomas of the kidney will be discussed.Due to the significantly divergent therapy, a correct diagnosis is important. Due to the often overlapping morphology, pathologic diagnosis is often difficult. In addition to the typical morphologic features, the specific immunohistochemical aspects as well as the known molecular changes will be presented.
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Affiliation(s)
- C Vokuhl
- Kindertumorregister der GPOH, Sektion Kinderpathologie, Institut für Pathologie, Universitätsklinikum SH, Campus Kiel, Arnold-Heller-Str. 10, Haus 4, 24105, Kiel, Deutschland.
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40
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Jackson TJ, Williams RD, Brok J, Chowdhury T, Ronghe M, Powis M, Pritchard-Jones K, Vujanić GM. The diagnostic accuracy and clinical utility of pediatric renal tumor biopsy: Report of the UK experience in the SIOP UK WT 2001 trial. Pediatr Blood Cancer 2019; 66:e27627. [PMID: 30761727 PMCID: PMC6522371 DOI: 10.1002/pbc.27627] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2018] [Revised: 11/19/2018] [Accepted: 12/06/2018] [Indexed: 01/13/2023]
Abstract
INTRODUCTION The International Society of Paediatric Oncology (SIOP) protocols recommend preoperative chemotherapy appropriate for Wilms tumors (WTs) in children with renal tumors aged ≥6 months, reserving biopsy for "atypical" cases. The Children's Cancer and Leukaemia Group (CCLG) joined the SIOP-WT-2001 study but continued the national practice of biopsy at presentation. METHOD Retrospective study of concordance between locally reported renal tumor biopsies and central pathology review nephrectomy diagnoses of children enrolled by CCLG centers in the SIOP-WT-2001 study. RESULTS Biopsy reports were available for 552/787 children with unilateral tumors. 36 of 552 (6.5%) were nondiagnostic: 2 normal tissue, 12 necrotic, 9 insufficient sample, and 13 indeterminate results (disproportionately non-WTs). The sensitivity and specificity of biopsy to identify tumors that did not require SIOP empirical preoperative chemotherapy were 86.0% and 99.6%, respectively. 13 of 548 (2.4%) biopsy results were discordant with nephrectomy; non-WTs other than renal cell carcinoma and clear cell sarcoma of the kidney (CCSK) were poorly recognized. In children aged 6-119 months, 480 of 518 (91.6%) had WT or nephroblastomatosis. 5 of 518 (1%) had benign tumors, and only one diagnosed on biopsy. Biopsy results correctly changed clinical management in 25 of 518 (4.8%), including identifying 19 of 20 CCSKs, but would have led to overtreatment in 5 of 518 (1%) or undertreatment in 4 of 518 (0.8%). In children aged ≥10 years, biopsy correctly changed management in 5 of 19 (26%) cases with no discordance. CONCLUSION Biopsy is less effective at identifying non-WTs than WTs and rarely changes management in younger children. Biopsy should be reserved in SIOP protocols for children ≥10 years and in younger children with clinical or radiological features inconsistent with WT.
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Affiliation(s)
- Thomas J Jackson
- University College London Great Ormond Street Institute of Child Health, London
| | - Richard D Williams
- University College London Great Ormond Street Institute of Child Health, London
| | - Jesper Brok
- University College London Great Ormond Street Institute of Child Health, London
- Department of Paediatric Oncology and Haematology, Rigshospitalet, Copenhagen, Denmark
| | - Tanzina Chowdhury
- University College London Great Ormond Street Institute of Child Health, London
- Department of Oncology, Great Ormond Street Hospital NHS Foundation Trust, London WC1N 3JH
| | - Milind Ronghe
- Department of Paediatric Oncology, Royal Hospital for Children, Glasgow
| | - Mark Powis
- Department of Paediatric Surgery, Leeds Teaching Hospital NHS Trust, Leeds
| | | | - Gordan M. Vujanić
- Department of Cellular Pathology, University Hospital of Wales, Cardiff, UK
- Department of Pathology, Sidra Medicine, Doha, Qatar
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Wang Z, Balgobind BV, Virgolin M, van Dijk IWEM, Wiersma J, Ronckers CM, Bosman PAN, Bel A, Alderliesten T. How do patient characteristics and anatomical features correlate to accuracy of organ dose reconstruction for Wilms' tumor radiation treatment plans when using a surrogate patient's CT scan? JOURNAL OF RADIOLOGICAL PROTECTION : OFFICIAL JOURNAL OF THE SOCIETY FOR RADIOLOGICAL PROTECTION 2019; 39:598-619. [PMID: 30965301 DOI: 10.1088/1361-6498/ab1796] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
In retrospective radiation treatment (RT) dosimetry, a surrogate anatomy is often used for patients without 3D CT. To gain insight in what the crucial aspects in a surrogate anatomy are to enable accurate dose reconstruction, we investigated the relation of patient characteristics and internal anatomical features with deviations in reconstructed organ dose using surrogate patient's CT scans. Abdominal CT scans of 35 childhood cancer patients (age: 2.1-5.6 yr; 17 boys, 18 girls) undergoing RT during 2004-2016 were included. Based on whether an intact right or left kidney is present in the CT scan, two groups were formed each containing 24 patients. From each group, four CTs associated with Wilms' tumor RT plans with an anterior-posterior-posterior-anterior field setup were selected as references. For each reference, a 2D digitally reconstructed radiograph was computed from the reference CT to simulate a 2D radiographic image and dose reconstruction was performed on the other CTs in the respective group. Deviations in organ mean dose (DEmean) of the reconstructions versus the references were calculated, as were deviations in patient characteristics (i.e. age, height, weight) and in anatomical features including organ volume, location (in 3D), and spatial overlaps. Per reference, the Pearson's correlation coefficient between deviations in DEmean and patient characteristics/features were studied. Deviation in organ locations and DEmean for the liver, spleen, and right kidney were moderately correlated (R2 > 0.5) for 8/8, 5/8, and 3/4 reference plans, respectively. Deviations in organ volume or spatial overlap and DEmean for the right and left kidney were weakly correlated (0.3 < R2 < 0.5) in 4/4 and 1/4 reference plans. No correlations (R2 < 0.3) were found between deviations in age or height and DEmean. Therefore, the performance of organ dose reconstruction using surrogate patients' CT scans is primarily related to deviation in organ location, followed by volume and spatial overlap. Further, results were plan dependent.
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Affiliation(s)
- Ziyuan Wang
- Department of Radiation Oncology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands
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Abstract
Clear cell sarcoma of the kidney is an uncommon malignant pediatric renal neoplasm that typically presents in the 2- to 3-year age group and has a propensity for aggressive behavior and late relapses. Histologically, this tumor exhibits a great diversity of morphologic patterns that can mimic most other pediatric renal neoplasms, often leading to confusion and misdiagnosis. Until recently, adjunct immunohistochemical and molecular genetic tests to support the diagnosis were lacking. The presence of internal tandem duplications in BCL-6 coreceptor (BCOR) and a translocation t(10;17) creating the fusion gene YWHAE-NUTM2B/E have now been well accepted. Immunohistochemistry for BCOR has also been shown to be a sensitive and specific marker for clear cell sarcoma of the kidney in the context of pediatric renal tumors. Improved intensive chemotherapy regimens have influenced the clinical course of the disease, with late relapses now being less frequent and the brain having overtaken bone as the most common site of relapse.
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Affiliation(s)
- Alessandro Pietro Aldera
- From the Division of Anatomical Pathology, University of Cape Town, Cape Town, and the National Health Laboratory Service, Western Cape, South Africa (Drs Aldera and Pillay); the Department of Anatomical Pathology, Groote Schuur Hospital, Western Cape, South Africa (Dr Aldera); and the Department of Anatomical Pathology, Red Cross War Memorial Children's Hospital, Cape Town, South Africa (Dr Pill
| | - Komala Pillay
- From the Division of Anatomical Pathology, University of Cape Town, Cape Town, and the National Health Laboratory Service, Western Cape, South Africa (Drs Aldera and Pillay); the Department of Anatomical Pathology, Groote Schuur Hospital, Western Cape, South Africa (Dr Aldera); and the Department of Anatomical Pathology, Red Cross War Memorial Children's Hospital, Cape Town, South Africa (Dr Pill
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BCOR-CCNB3 Fusion Positive Sarcomas: A Clinicopathologic and Molecular Analysis of 36 Cases With Comparison to Morphologic Spectrum and Clinical Behavior of Other Round Cell Sarcomas. Am J Surg Pathol 2019; 42:604-615. [PMID: 29300189 DOI: 10.1097/pas.0000000000000965] [Citation(s) in RCA: 178] [Impact Index Per Article: 29.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BCOR-CCNB3 sarcoma (BCS) is a recently defined genetic entity among undifferentiated round cell sarcomas, which was initially classified as and treated similarly to the Ewing sarcoma (ES) family of tumors. In contrast to ES, BCS shows consistent BCOR overexpression, and preliminary evidence suggests that these tumors share morphologic features with other tumors harboring BCOR genetic alterations, including BCOR internal tandem duplication (ITD) and BCOR-MAML3. To further investigate the pathologic features, clinical behavior, and their relationship to other round cell sarcomas, we collected 36 molecularly confirmed BCSs for a detailed histologic and immunohistochemical analysis. Four of the cases were also analyzed by RNA sequencing (RNAseq). An additional case with BCOR overexpression but negative CCNB3 abnormality showed a novel KMT2D-BCOR fusion by targeted RNAseq. The patients ranged in age from 2 to 44 years old (mean and median, 15), with striking male predominance (M:F=31:5). The tumor locations were slightly more common in bone (n=20) than soft tissue (n=14), with rare visceral (kidney, n=2) involvement. Histologically, BCS showed a spectrum of round to spindle cells with variable cellularity, monomorphic nuclei and fine chromatin pattern, delicate capillary network, and varying amounts of myxoid or collagenous stroma. The morphologic features and immunoprofile showed considerable overlap with other round cell sarcomas with BCOR oncogenic upregulation, that is, BCOR-MAML3 and BCOR ITD. Follow-up available in 22 patients showed a 5-year overall survival of 72%, which was relatively similar to ES (79%, P=0.738) and significantly better than CIC-DUX4 sarcomas (43%, P=0.005) control groups. Local recurrences occurred in 6 patients and distant metastases (lung, soft tissue/bone, pancreas) in 4. Seven of 9 cases treated with an ES chemotherapy regimen with evaluable histologic response showed >60% necrosis in posttherapy resections. Unsupervised clustering by RNAseq data revealed that tumors with BCOR genetic alterations, including BCOR-CCNB3, BCOR-MAML3, and BCOR ITD, formed a tight genomic group distinct from ES and CIC-rearranged sarcomas.
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Wang JH, Li MJ, Tang DX, Xu S, Mao JQ, Cai JB, He M, Shu Q, Lai C. Neoadjuvant transcatheter arterial chemoembolization and systemic chemotherapy for treatment of clear cell sarcoma of the kidney in children. J Pediatr Surg 2019; 54:550-556. [PMID: 30318310 DOI: 10.1016/j.jpedsurg.2018.09.012] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2017] [Revised: 08/27/2018] [Accepted: 09/24/2018] [Indexed: 12/18/2022]
Abstract
BACKGROUND Clear cell sarcoma of the kidney (CCSK) is a rare and aggressive malignant renal tumor. We describe our experience with neoadjuvant transcatheter arterial chemoembolization (TACE) and systematic chemotherapy for the treatment of advanced CCSK in children. METHODS Between January 2010 and December 2016, seven patients (3 boys and 4 girls; median 2.2 years) with advanced CCSK received preoperative TACE of renal artery and systemic chemotherapy. The chemoembolic emulsion for TACE consisted of cisplatin, pirarubicin, vindesine, and iodized oil. Preoperative systemic chemotherapy with vindesine, ifosfamide, and etoposide was administered three weeks after TACE. Nephrectomy was performed three weeks after systemic chemotherapy. After surgery, patients received radiotherapy and postoperative chemotherapy. RESULTS No cardiotoxicity, renal insufficiency, or hepatic dysfunction was found in any patients. Grade II-III marrow suppression developed in four patients. One patient with tumor progress during neoadjuvant therapy failed to successfully undergo surgery and died. Six patients underwent nephrectomy after neoadjuvant therapy. Median follow-up period was 49.5 months (range, 11-83 months). Five patients have recurrence-free survival. One patient is still in postoperative chemotherapy after nephrectomy, radiotherapy and thoracoscopic resection of lung metastases. CONCLUSIONS Neoadjuvant TACE and systemic chemotherapy appeared to be feasible in the treatment of advanced CCSK in this pilot study. THE TYPE OF STUDY A case series with no comparison group. LEVEL OF EVIDENCE Level IV.
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Affiliation(s)
- Jin-Hu Wang
- Division of Surgical Oncology, Department of Pediatric Surgery, The Children's Hospital, Zhejiang University School of Medicine, No. 3333 Binsheng Road, 310052 Hangzhou, China.
| | - Min-Ju Li
- Division of Surgical Oncology, Department of Pediatric Surgery, The Children's Hospital, Zhejiang University School of Medicine, No. 3333 Binsheng Road, 310052 Hangzhou, China.
| | - Da-Xing Tang
- Division of pediatric urology, Department of Pediatric Surgery, The Children's Hospital, Zhejiang University School of Medicine, No. 3333 Binsheng Road, 310052 Hangzhou, China.
| | - Shan Xu
- Division of pediatric urology, Department of Pediatric Surgery, The Children's Hospital, Zhejiang University School of Medicine, No. 3333 Binsheng Road, 310052 Hangzhou, China.
| | - Jun-Qing Mao
- Division of Surgical Oncology, Department of Pediatric Surgery, The Children's Hospital, Zhejiang University School of Medicine, No. 3333 Binsheng Road, 310052 Hangzhou, China.
| | - Jia-Bin Cai
- Division of Surgical Oncology, Department of Pediatric Surgery, The Children's Hospital, Zhejiang University School of Medicine, No. 3333 Binsheng Road, 310052 Hangzhou, China.
| | - Min He
- Division of Surgical Oncology, Department of Pediatric Surgery, The Children's Hospital, Zhejiang University School of Medicine, No. 3333 Binsheng Road, 310052 Hangzhou, China.
| | - Qiang Shu
- Division of Surgical Oncology, Department of Pediatric Surgery, The Children's Hospital, Zhejiang University School of Medicine, No. 3333 Binsheng Road, 310052 Hangzhou, China.
| | - Can Lai
- Department of Radiology, The Children's Hospital, Zhejiang University School of Medicine, No. 3333 Binsheng Road, 310052 Hangzhou, China.
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Uddin N, Minhas K, Abdul-Ghafar J, Ahmed A, Ahmad Z. Expression of cyclin D1 in clear cell sarcoma of kidney. Is it useful in differentiating it from its histological mimics? Diagn Pathol 2019; 14:13. [PMID: 30736802 PMCID: PMC6368701 DOI: 10.1186/s13000-019-0790-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2018] [Accepted: 02/01/2019] [Indexed: 01/14/2023] Open
Abstract
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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Affiliation(s)
- Nasir Uddin
- Department of Pathology and Laboratory Medicine, Aga Khan University Hospital, Karachi, Pakistan
| | - Khurram Minhas
- Department of Pathology and Laboratory Medicine, Aga Khan University Hospital, Karachi, Pakistan
| | - Jamshid Abdul-Ghafar
- Department of Pathology and Laboratory Medicine, French Medical Institute for Mothers and Children (FMIC), Kabul, Afghanistan
| | - Arsalan Ahmed
- Department of Pathology and Laboratory Medicine, Aga Khan University Hospital, Karachi, Pakistan
| | - Zubair Ahmad
- Department of Pathology and Laboratory Medicine, Aga Khan University Hospital, Karachi, Pakistan
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Abstract
Clear cell sarcoma of the kidney is the second most common primary renal malignancy in childhood. It is histologically diverse, making accurate diagnosis challenging in some cases. Recent molecular studies have uncovered BCOR exon 15 internal tandem duplications in most cases, and YWHAE-NUTM2 fusion in a few cases, with the remaining cases having other genetic mutations, including BCOR-CCNB3 fusion and EGFR mutations. Although clear cell sarcoma of the kidney has no specific immunophenotype, several markers including cyclin D1, nerve growth factor receptor, and BCOR (BCL6 corepressor) have emerged as potential diagnostic aides. This review provides a concise account of recent advances in our understanding of clear cell sarcoma of the kidney to serve as a practical update for the practicing pathologist.
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Affiliation(s)
- Sze Jet Aw
- From the Department of Pathology and Laboratory Medicine, KK Women's and Children's Hospital, Singapore, Republic of Singapore
| | - Kenneth Tou En Chang
- From the Department of Pathology and Laboratory Medicine, KK Women's and Children's Hospital, Singapore, Republic of Singapore
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47
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Seibel NL, Chi YY, Perlman EJ, Tian J, Sun J, Anderson JR, Ritchey ML, Thomas PR, Miser J, Kalapurakal JA, Grundy PE, Green DM. Impact of cyclophosphamide and etoposide on outcome of clear cell sarcoma of the kidney treated on the National Wilms Tumor Study-5 (NWTS-5). Pediatr Blood Cancer 2019; 66:e27450. [PMID: 30255545 PMCID: PMC6249042 DOI: 10.1002/pbc.27450] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2018] [Revised: 08/10/2018] [Accepted: 08/11/2018] [Indexed: 12/28/2022]
Abstract
PURPOSE To improve the event-free survival (EFS) and overall survival (OS) for patients with clear cell sarcoma of the kidney (CCSK) by incorporating cyclophosphamide and etoposide into treatment on National Wilms Tumor Study (NWTS)-5. PATIENTS AND METHODS Patients less than 16 years of age with a centrally confirmed pathological diagnosis of CCSK were eligible for treatment on this prospective single-arm study conducted between August 1995 and June 2002. Staging consisted of CT scans of chest, abdomen, pelvis, bone scan, skeletal survey, and CT or MRI of the head. Treatment consisted of vincristine/doxorubicin/cyclophosphamide alternating with cyclophosphamide/etoposide for 24 weeks and radiation to sites of disease. RESULTS One hundred eight eligible patients were enrolled on study (69% males, 63% Caucasian), with a median age of 22 months. Stage distribution was as follows: stage I, 12; II, 44; III, 45; IV, 7. Median follow-up was 9.7 years. Five-year EFS and OS were 79% (95% CI: 71%-88%) and 90% (95% CI: 84%-96%). Five-year EFS for stage I-IV was 100%, 88%, 73%, and 29%, respectively. Twenty of the 23 disease-related events occurred within three years of initial treatment. The most common site of recurrence was brain (12/23). CONCLUSION The outcome for patients with CCSK treated on NWTS-5 was similar to NWTS-4 and accomplished over a shorter treatment duration. Stage was highly predictive of outcome. Brain metastases occurred more frequently than on NWTS-4. Regimen I showed more benefit for patients with stage I and II disease as compared with higher stages of disease where new therapies are needed.
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Affiliation(s)
- Nita L. Seibel
- Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD; George Washington University School of Medicine and Health Science, Washington, DC
| | - Yueh-Yun Chi
- Department of Biostatistics, University of Florida, Gainesville, FL
| | | | - Jing Tian
- Department of Biostatistics, University of Florida, Gainesville, FL
| | - Junfeng Sun
- Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD
| | | | | | | | - James Miser
- City of Hope National Medical Center, Duarte, CA
| | - John A Kalapurakal
- Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL
| | - Paul E. Grundy
- Department of Pediatrics and Oncology, University of Alberta, Edmonton, Alberta, Canada
| | - Daniel M. Green
- Department of Epidemiology and Cancer Control, St Jude Children’s Research Hospital, Memphis, TN
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Ueno-Yokohata H, Okita H, Nakasato K, Hishiki T, Shirai R, Tsujimoto S, Osumi T, Yoshimura S, Yamada Y, Shioda Y, Kiyotani C, Terashima K, Miyazaki O, Matsumoto K, Kiyokawa N, Yoshioka T, Kato M. Preoperative diagnosis of clear cell sarcoma of the kidney by detection of BCOR internal tandem duplication in circulating tumor DNA. Genes Chromosomes Cancer 2018; 57:525-529. [PMID: 30126017 DOI: 10.1002/gcc.22648] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2018] [Revised: 06/06/2018] [Accepted: 06/06/2018] [Indexed: 01/06/2023] Open
Abstract
Clear cell sarcoma of the kidney (CCSK) is the second most common renal malignancy in children. The prognosis is poorer in CCSK than in Wilms' tumor, and multimodal treatment including surgery, intensive chemotherapy, and radiation is required to improve the outcome for children with CCSK. Histological evaluation is required for the diagnosis. However, biopsies of tumors to obtain diagnostic specimens are not routinely performed because of the risk of spreading tumor cells during the procedure. Recently, internal tandem duplication (ITD) of BCOR has been recognized as a genetic hallmark of CCSK. We herein established a novel BCOR-ITD-specific polymerase chain reaction method with well-designed primers, and then performed a liquid biopsy for cell-free DNA (cfDNA) obtained from plasma of three children with nonmetastatic renal tumors (stage II) and from one control. BCOR-ITD was positively detected in the cfDNA of two cases, both of which were later diagnosed as CCSK based on histological feature of the resected tumor specimen, while it was not detected for a normal control and a patient diagnosed with Wilms' tumor. Our study is the first one of preoperative circulating tumor DNA assay in pediatric renal tumors. The liquid biopsy method enables less invasive, preoperative diagnosis of CCSK with no risk of tumor spillage, which can avoid iatrogenic upstaging.
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Affiliation(s)
- Hitomi Ueno-Yokohata
- Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Tokyo, Japan
| | - Hajime Okita
- Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Tokyo, Japan.,Department of Pathology, Keio University School of Medicine, Tokyo, Japan.,Department of Pathology, National Center for Child Health and Development, Tokyo, Japan
| | - Keiko Nakasato
- Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Tokyo, Japan
| | - Tomoro Hishiki
- Division of Surgical Oncology, Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan
| | - Ryota Shirai
- Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Tokyo, Japan
| | - Shinichi Tsujimoto
- Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Tokyo, Japan
| | - Tomoo Osumi
- Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Tokyo, Japan.,Division of Leukemia and Lymphoma/Solid Tumor, Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan
| | - Satoshi Yoshimura
- Division of Leukemia and Lymphoma/Solid Tumor, Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan
| | - Yuji Yamada
- Division of Leukemia and Lymphoma/Solid Tumor, Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan
| | - Yoko Shioda
- Division of Leukemia and Lymphoma/Solid Tumor, Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan
| | - Chikako Kiyotani
- Division of Leukemia and Lymphoma/Solid Tumor, Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan
| | - Keita Terashima
- Division of Neuro-Oncology, Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan
| | - Osamu Miyazaki
- Department of Radiology, National Center for Child Health and Development, Tokyo, Japan
| | - Kimikazu Matsumoto
- Division of Leukemia and Lymphoma/Solid Tumor, Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan.,Division of Neuro-Oncology, Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan.,Division of Stem Cell Transplantation and Cellular Therapy, Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan
| | - Nobutaka Kiyokawa
- Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Tokyo, Japan.,Department of Pathology, National Center for Child Health and Development, Tokyo, Japan
| | - Takako Yoshioka
- Department of Pathology, National Center for Child Health and Development, Tokyo, Japan
| | - Motohiro Kato
- Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Tokyo, Japan.,Division of Stem Cell Transplantation and Cellular Therapy, Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan
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Koshinaga T, Takimoto T, Oue T, Okita H, Tanaka Y, Nozaki M, Tsuchiya K, Inoue E, Haruta M, Kaneko Y, Fukuzawa M. Outcome of renal tumors registered in Japan Wilms Tumor Study-2 (JWiTS-2): A report from the Japan Children's Cancer Group (JCCG). Pediatr Blood Cancer 2018; 65:e27056. [PMID: 29630767 DOI: 10.1002/pbc.27056] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2017] [Revised: 02/12/2018] [Accepted: 02/20/2018] [Indexed: 11/07/2022]
Abstract
BACKGROUND Japan Wilms Tumor Study-2 (JWiTS-2) mandated central pathology review for all case registrations. The study aimed to compare the outcomes of patients with unilateral Wilms tumor enrolled on the JWiTS-1 and JWiTS-2 trials. PROCEDURE The JWiTS-2 trial (2006-2014), a prospective, single-arm study, required compulsory submission of histologic slides to central pathology, while in the JWiTS-1 trial, such submission was not compulsory. Relapse-free survival (RFS) and overall survival (OS) versus cases in the JWiTS-1 trial (1996-2005) were statistically evaluated. RESULTS Of 277 enrolled patients with primary renal tumors diagnosed by the central pathology review system, 225 patients with unilateral renal tumors were followed up over 9 years. The RFS and OS of Wilms tumor (n = 178) were 90.4% (P = 0.0003) and 96.8% (P = 0.054), respectively, as compared to 74.9% and 89.4% in JWiTS-1. RFS rates of stages I-III Wilms tumor in JWiTS-2 were more than 90%, although the outcome of stage IV Wilms tumor was significantly poorer (RFS: 66.2%) (P = 0.0094). RFS and OS of clear cell sarcoma of the kidney (CCSK; n = 31) were 82.4% (P = 0.30) and 91.3% (P = 0.42), respectively, as compared to 68.8% and 81.3% in JWiTS-1, and those of rhabdoid tumor of the kidney (RTK; n = 16) were 18.8% (P = 0.88) and 25.0% (P = 0.80), respectively, as compared to 23.5% and 23.5% in JWiTS-1. CONCLUSIONS RFS and OS for stages I-III Wilms tumor were improved in JWiTS-2 compared to JWiTS-1, whereas outcomes for stage IV Wilms tumor, CCSK, and RTK did not improve.
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Affiliation(s)
- Tsugumichi Koshinaga
- Department of Pediatric Surgery, Nihon University School of Medicine, Tokyo, Japan
| | - Tetsuya Takimoto
- Division of Registration and Research for Childhood Cancer, National Center for Child Health and Development, Tokyo, Japan
| | - Takaharu Oue
- Department of Pediatric Surgery, Hyogo College of Medicine, Nishinomiya, Japan
| | - Hajime Okita
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan.,Department of Pediatric Hematology and Oncology Research, Research Institute, National Center for Child Health and Development, Tokyo, Japan
| | - Yukichi Tanaka
- Department of Pathology and Clinical Research Institute, Kanagawa Children's Medical Center, Yokohama, Japan
| | - Miwako Nozaki
- Department of Radiology, Dokkyo Medical University Saitama Medical Center, Koshigaya, Japan
| | - Kunihiko Tsuchiya
- Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Eisuke Inoue
- Division of Medical Informatics, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Masayuki Haruta
- Research Institute for Clinical Oncology, Saitama Cancer Center, Kitaadachi-gun, Japan
| | - Yasuhiko Kaneko
- Research Institute for Clinical Oncology, Saitama Cancer Center, Kitaadachi-gun, Japan
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50
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Lang A, Dehner LP. Delayed Metastasis of Clear Cell Sarcoma of Kidney to Bladder After 7 Disease-Free Years. Fetal Pediatr Pathol 2018; 37:126-133. [PMID: 29509095 DOI: 10.1080/15513815.2018.1435757] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
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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Affiliation(s)
- Adam Lang
- a Lauren V. Ackerman Laboratory of Surgical Pathology, Barnes-Jewish Hospital/St. Louis Children's Hospital , Washington University Medical Center , St. Louis , Missouri , USA
| | - Louis P Dehner
- a Lauren V. Ackerman Laboratory of Surgical Pathology, Barnes-Jewish Hospital/St. Louis Children's Hospital , Washington University Medical Center , St. Louis , Missouri , USA
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