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In Vivo (Athens, Greece) 2021Recent studies suggest that not only the nephrogenic blastema but also the ureteric bud is involved in oncogenesis of Wilms' tumor (WT). However, the occurrence of...
BACKGROUND/AIM
Recent studies suggest that not only the nephrogenic blastema but also the ureteric bud is involved in oncogenesis of Wilms' tumor (WT). However, the occurrence of ureteric bud (UB) derivatives in nephrogenic rest is not yet known. The aim of our study was to find UB derivatives in WT.
MATERIALS AND METHODS
Keratin 17 (KRT17) is expressed exclusively in UB in foetal kidneys. In this study KRT17 immunohistochemistry was used to detect UB-derivatives in 21 triphasic, 2 stromal and 3 epithelial predominant WTs and 9 nephrogenic rests.
RESULTS
We have detected KRT17 positive tubular structures resembling UB in 3 of 9 nephrogenic rests and 15 of 26 WTs.
CONCLUSION
Not only the metanephric blastema but also the UB is involved in the histogenesis of nephrogenic rest and WT.
Topics: Cell Transformation, Neoplastic; Humans; Immunohistochemistry; Kidney; Kidney Neoplasms; Wilms Tumor
PubMed: 34182492
DOI: 10.21873/invivo.12486 -
Journal of Magnetic Resonance Imaging :... Feb 2022The SIOP-Renal Tumor Study Group (RTSG) does not advocate invasive procedures to determine histology before the start of therapy. This may induce misdiagnosis-based...
BACKGROUND
The SIOP-Renal Tumor Study Group (RTSG) does not advocate invasive procedures to determine histology before the start of therapy. This may induce misdiagnosis-based treatment initiation, but only for a relatively small percentage of approximately 10% of non-Wilms tumors (non-WTs). MRI could be useful for reducing misdiagnosis, but there is no global consensus on differentiating characteristics.
PURPOSE
To identify MRI characteristics that may be used for discrimination of newly diagnosed pediatric renal tumors.
STUDY TYPE
Consensus process using a Delphi method.
POPULATION
Not applicable.
FIELD STRENGTH/SEQUENCE
Abdominal MRI including T1- and T2-weighted imaging, contrast-enhanced MRI, and diffusion-weighted imaging at 1.5 or 3 T.
ASSESSMENT
Twenty-three radiologists from the SIOP-RTSG radiology panel with ≥5 years of experience in MRI of pediatric renal tumors and/or who had assessed ≥50 MRI scans of pediatric renal tumors in the past 5 years identified potentially discriminatory characteristics in the first questionnaire. These characteristics were scored in the subsequent second round, consisting of 5-point Likert scales, ranking- and multiple choice questions.
STATISTICAL TESTS
The cut-off value for consensus and agreement among the majority was ≥75% and ≥60%, respectively, with a median of ≥4 on the Likert scale.
RESULTS
Consensus on specific characteristics mainly concerned the discrimination between WTs and non-WTs, and WTs and nephrogenic rest(s) (NR)/nephroblastomatosis. The presence of bilateral lesions (75.0%) and NR/nephroblastomatosis (65.0%) were MRI characteristics indicated as specific for the diagnosis of a WT, and 91.3% of the participants agreed that MRI is useful to distinguish NR/nephroblastomatosis from WT. Furthermore, all participants agreed that age influenced their prediction in the discrimination of pediatric renal tumors.
DATA CONCLUSION
Although the discrimination of pediatric renal tumors based on MRI remains challenging, this study identified some specific characteristics for tumor subtypes, based on the shared opinion of experts. These results may guide future validation studies and innovative efforts.
LEVEL OF EVIDENCE
3 Technical Efficacy Stage: 3.
Topics: Delphi Technique; Diffusion Magnetic Resonance Imaging; Humans; Kidney Neoplasms; Radiology; Wilms Tumor
PubMed: 34363274
DOI: 10.1002/jmri.27878 -
AJR. American Journal of Roentgenology May 2020Distinguishing nephrogenic rests from small Wilms tumors can be challenging. This retrospective study was performed to determine if imaging characteristics can be used...
Distinguishing nephrogenic rests from small Wilms tumors can be challenging. This retrospective study was performed to determine if imaging characteristics can be used to distinguish nephrogenic rests from Wilms tumors. All cases of pathologically confirmed nephrogenic rests and Wilms tumors smaller than 5 cm in maximum dimension on imaging in patients younger than 5 years old were identified from the Children's Oncology Group AREN03B2 study (July 2006-August 2016). Exclusion criteria were chemotherapy before pathologic evaluation or more than 30 days between imaging and surgery; in addition, patients with nephrogenic rests occurring within or juxtaposed to a Wilms tumor and patients with diffuse hyperplastic perilobar nephroblastomatosis were excluded. Two radiologists who were blinded to pathology results assessed all lesions. The two-sample test was used for continuous variables, and the Fisher exact test was used for categoric variables. ROC analysis was performed to determine the optimal size cutoff for distinguishing between nephrogenic rests and Wilms tumors. Thirty-one pathologically confirmed rests (20 perilobar, 11 intralobar) and 26 Wilms tumors smaller than 5 cm met the eligibility criteria for study inclusion. The median diameter of the nephrogenic rests was 1.3 cm (range, 0.7-3.4 cm) and the median diameter of the Wilms tumor was 3.2 cm (range, 1.8-4.9 cm) ( < 0.001). Imaging findings supportive of Wilms tumors were spherical ( < 0.001) and exophytic ( < 0.001) lesions. Perilobar rests (17/20) were more likely to be homogeneous than intralobar rests (3/11) or Wilms tumor (3/26) ( < 0.001). ROC analysis showed that the optimal size cutoff for distinguishing between nephrogenic rests and Wilms tumors was 1.75 cm. In children younger than 5 years old, the diagnosis of a Wilms tumor should be favored over a nephrogenic rest when a renal mass is spherical, exophytic, or larger than 1.75 cm. Homogeneity favors the diagnosis of perilobar nephrogenic rests, whereas intralobar rests and Wilms tumors are more likely to be inhomogeneous.
Topics: Child, Preschool; Diagnosis, Differential; Female; Humans; Infant; Kidney; Kidney Neoplasms; Male; Precancerous Conditions; Retrospective Studies; Wilms Tumor
PubMed: 32160052
DOI: 10.2214/AJR.19.22301 -
Annals of Saudi Medicine May 2012Ectopic nephrogenic rests in the inguinal canal are rare. Usually discovered incidentally during surgery, these rests should raise the suspicion of an early extrarenal...
Ectopic nephrogenic rests in the inguinal canal are rare. Usually discovered incidentally during surgery, these rests should raise the suspicion of an early extrarenal Wilms tumor. The differential diagnosis between the two entities is not only difficult but also essential, since they imply different treatment decisions. We report a rare case of an inguinal ectopic nephrogenic rest found in a 6-month-old girl and discuss the clinicopathological implications of this condition. The patient was admitted for a routine repair of a presumed inguinal hernia; during surgery, a nodular mass was noted in the inguinal canal. Pathological diagnosis confirmed the diagnosis of an extrarenal hyperplastic nephrogenic rest. Five previous cases of ectopic nephrogenic rests originating in the inguinal canal have been reported, all of which were associated with a patent processus vaginalis. In this case, the nephrogenic rest was not associated with a congenital inguinal hernia.
PubMed: 22634548
DOI: 10.5144/0256-4947.2012.23.5.1126 -
International Journal of Biological... 2018We have suggested that papillary renal cell tumor (PRCT) of the kidney arises from nephrogenic rest-like lesions. To approve our hypothesis, we worked up 14 kidneys...
We have suggested that papillary renal cell tumor (PRCT) of the kidney arises from nephrogenic rest-like lesions. To approve our hypothesis, we worked up 14 kidneys bearing papillary and 14 ones with conventional renal cell carcinoma (CRCC) histologically and found 42 papillary lesions in average per kidney bearing PRCT. PRCTs are characterized by loss of the Y chromosome and trisomy of chromosomes 7 and 17. The and are localized to chromosome 7q31 and 17q21 and are frequently amplified in PRCT. We have analyzed the expression of the mutant in hereditary PRCTs and precursor lesions and found duplication and expression of the mutated allele. Because both genes are involved in early stage of nephron development, we have analyzed the expression of and by immunohistochemistry in fetal kidneys, precursor lesions and PRCTs. We detected strong expression of and in distal compartment of S-shaped body of fetal kidneys and in nephrogenic rest-like precursor lesions. Our finding suggests an association between expression of and in precursor lesions and development of PRCT. We propose a model involving chromosomal clonal evolution and corresponding gene expression for development of PRCTs from embryonic rests due to impaired differentiation. Our model suggests that PRCT have a natural history distinct from that of most common CRCC.
Topics: Alleles; Carcinogenesis; Carcinoma, Renal Cell; Cell Transformation, Neoplastic; Female; Hepatocyte Nuclear Factor 1-beta; Humans; Kidney; Kidney Neoplasms; Male
PubMed: 29910688
DOI: 10.7150/ijbs.22489 -
The American Journal of Pathology Sep 1998Nephrogenic rests are precursor lesions associated with about 40% of Wilms' tumors. This study identifies genetic steps occurring in the development of Wilms' tumor....
Nephrogenic rests are precursor lesions associated with about 40% of Wilms' tumors. This study identifies genetic steps occurring in the development of Wilms' tumor. Thirty-four Wilms' tumors with nephrogenic rests and/or areas of anaplasia were microdissected from paraffin sections to determine whether and at what stage loss of heterozygosity (LOH) occurred, using polymerase chain reaction-based polymorphic markers at 11p13, 11p15, and 16q. LOH at these loci have been identified in Wilms' tumors and are associated with identified or putative tumor suppressor genes. Three cystic nephromas/cystic partially differentiated nephroblastomas were also examined. LOH was detected in six cases at 11p13 and in six cases at 11p15, and two of these cases had LOH at both loci. All intralobar rests showing LOH also showed LOH in the tumor. A case with a small perilobar rest showed LOH of 11p13 only in the tumor. Five cases showing LOH at 16q were identified (this was identified only in the tumor, and not in the associated rest), and three of these had recurrence of the tumor. Two cases had a WT1 mutation (one germline and the other somatic), as well as LOH in both the intralobar rest and the tumor. A cystic partially differentiated nephroblastoma showed loss at 11p13 and 11p15, as well as at 16q. This study suggests that LOH at 11p13 and 11p15 and WT1 mutations are early events but that LOH at 16q occurs late in the pathogenesis of Wilms' tumor. Intralobar and perilobar nephrogenic rests are known to have different biological behaviors, and this study suggests that they are genetically different. A multistep model of Wilms' tumor pathogenesis is supported by these findings.
Topics: Adolescent; Child, Preschool; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 16; DNA Primers; DNA, Neoplasm; DNA-Binding Proteins; Disease Progression; Female; Genes, Wilms Tumor; Humans; Infant; Kidney; Kidney Neoplasms; Loss of Heterozygosity; Male; Polymerase Chain Reaction; Precancerous Conditions; Transcription Factors; WT1 Proteins; Wilms Tumor
PubMed: 9736048
DOI: 10.1016/S0002-9440(10)65641-6 -
Asian Journal of Surgery Apr 2021
Topics: Adult; Humans; Kidney Neoplasms; Rest
PubMed: 33632553
DOI: 10.1016/j.asjsur.2021.01.015 -
Pediatric Blood & Cancer Nov 2017Nephrogenic rests (NRs) are abnormally persistent foci of embryonal cells, thought to be the precursor lesion of Wilms tumors (WTs). To date, their presence has not been...
BACKGROUND
Nephrogenic rests (NRs) are abnormally persistent foci of embryonal cells, thought to be the precursor lesion of Wilms tumors (WTs). To date, their presence has not been systematically examined in WTs treated with preoperative chemotherapy.
METHODS
A systematic analysis of the data on NRs in WTs treated with preoperative chemotherapy obtained from the UK cohort of the International Society of Pediatric Oncology (SIOP) WT 2001 Trial. The study was based on central pathology review of full sets of slides from pathological specimens, with a median of 28 slides reviewed per case.
RESULTS
NRs were identified in 40% of unilateral WTs, including 25% perilobar nephrogenic rest (PLNR), 9% intralobar nephrogenic rest (ILNR), 5% both PLNR and ILNR, and 1% nephroblastomatosis, and in 93% of cases with bilateral lesions. ILNRs were associated with stromal histology and a younger age at diagnosis and found frequently in patients with congenital anomalies associated with WT1 mutation. PLNRs were found frequently in patients with overgrowth syndromes.
CONCLUSIONS
The prevalence of NRs in WTs after preoperative chemotherapy observed in SIOP UK WT 2001 Trial is similar to the previously published data on NRs not treated with preoperative chemotherapy. Their epidemiology supports at least two pathways to Wilms tumorigenesis.
Topics: Antineoplastic Agents; Follow-Up Studies; Humans; International Agencies; Kidney Neoplasms; Neoplasm Staging; Preoperative Care; Prevalence; Prognosis; United Kingdom; Wilms Tumor
PubMed: 28383760
DOI: 10.1002/pbc.26547 -
Journal of Pediatric Surgery Nov 2008We reviewed the long-term local tumor control in patients with bilateral Wilm's tumor (BWT) who received no definitive surgical therapy to one kidney after complete...
PURPOSE
We reviewed the long-term local tumor control in patients with bilateral Wilm's tumor (BWT) who received no definitive surgical therapy to one kidney after complete radiographic resolution after initial chemotherapy.
METHODS
National Wilm's Tumor Study 4 (NWTS-4) enrolled 3335 patients (pts) during the period August 1986 to August 1994. There were 188 pts with BWT or 5.6% of the total enrolled. The treatment records and imaging reports were reviewed to ascertain those children who had documented tumors without definitive surgical therapy after initial treatment. Patients who did not have renal surgery because of progression of tumor were excluded from this study.
RESULTS
Eleven children had no definitive surgical treatment of renal lesions in one kidney (right, 6; left, 5) after initial treatment with chemotherapy and/or radiation therapy. The pretreatment size of the lesions were less than 3 cm (4 pts), 3 to 6 cm (5 pts), more than 6 cm (1 pt), and unknown (1 pt). Prechemotherapy biopsy was performed in 6 of 11 patients. Lesions were less than 3 cm (1 pt), 3 to 6 cm (3 pts), more than 6 cm (1 pt), and unknown (1 pt). Four biopsy specimens showed favorable Wilm's histologic findings. One lesion (4 cm) showed an intralobar nephrogenic rest, another lesion of unknown size was read as favorable histologic findings vs perilobar nephrogenic rest. Biopsy was not performed on 5 lesions (4 pts, <1 cm; 1 pt, 3cm). Only 2 children in this study received radiation treatment. One child received 1050 cGy whole abdominal radiation, and 1 child received 1060 cGy to the left flank postnephrectomy. Radiation therapy was not given to any patient because of failure of the tumor to respond to chemotherapy. Five patients received treatment regimen EE-4A, dactinomycin, and vincristine. The duration of therapy ranged from 24 to 102 weeks for an average of 55.6 weeks. Three patients received treatment regimen DD-4A, dactinomycin, vincristine, and doxorubicin for 28, 52, and 52 weeks, respectively. Three patients received 2 separate regimens of chemotherapy. One child was treated with dactinomycin, vincristine, and cyclophosphamide for 60 weeks and then received regimen EE-4A for 24 weeks. Another patient received regimen EE-4A for 16 weeks and then regimen DD4-A for 36 weeks. One child received regimen EE-4-A for 12 weeks and then regimen DD4A for 40 weeks. Management of the contralateral kidney was complete nephrectomy in all 11 patients. There were no local relapses in the renal tumor bed. All patients were alive at a median follow-up of 9 years (range, 9 months to 15 years).
CONCLUSION
Children with synchronous BWT or Wilm's tumor and contralateral nephrogenic rests that have radiographic resolution, after initial treatment, have a low risk for local relapse. These children should be followed by serial imaging.
Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Cyclophosphamide; Dactinomycin; Doxorubicin; Follow-Up Studies; Humans; Kidney Neoplasms; Neoplasms, Multiple Primary; Nephrectomy; Radiography; Radiotherapy, Adjuvant; Remission Induction; Retrospective Studies; Treatment Outcome; Vincristine; Wilms Tumor
PubMed: 18970928
DOI: 10.1016/j.jpedsurg.2008.05.037