Case Of Wilms Research Articles

Low risk of embryonic and other cancers in PIK3CA-related overgrowth spectrum: Impact on screening recommendations.

The PIK3CA-related overgrowth spectrum (PROS) encompasses various conditions caused by mosaic activating PIK3CA variants. PIK3CA somatic variants are also involved in various cancer types. Some generalized overgrowth syndromes are associated with an increased risk of Wilms tumor (WT). In PROS, abdominal ultrasound surveillance has been advocated to detect WT. We aimed to determine the risk of embryonic and other types of tumors in patients with PROS in order to evaluate surveillance relevance. We searched the clinical charts from 267 PROS patients for the diagnosis of cancer, and reviewed the medical literature for the risk of cancer. In our cohort, six patients developed a cancer (2.2%), and Kaplan Meier analyses estimated cumulative probabilities of cancer occurrence at 45 years of age was 5.6% (95% CI = 1.35%-21.8%). The presence of the PIK3CA variant was only confirmed in two out of four tumor samples. In the literature and our cohort, six cases of Wilms tumor/nephrogenic rests (0.12%) and four cases of other cancers have been reported out of 483 proven PIK3CA patients, in particular the p.(His1047Leu/Arg) variant. The risk of WT in PROS being lower than 5%, this is insufficient evidence to recommend routine abdominal imaging. Long-term follow-up studies are needed to evaluate the risk of other cancer types, as well as the relationship with the extent of tissue mosaicism and the presence or not of the variant in the tumor samples.

Friend or foe? The case of Wilms' Tumor 1 (WT1) mutations in acute myeloid leukemia

Wilms tumor 1 (WT1) gene is commonly mutated in acute myeloid leukemia (AML), particularly in younger age population. The mechanism through which WT1 mutations drive leukemogenesis have not been fully elucidated; however, recent studies reported an association with the epigenetic pathway. Here, we studied the phenotypic characteristics and somatic mutational profile of 114 WT1-mutant AML patients and focused on potential WT1 gene relations to other cooperative genomic events that may impact disease prognosis. Invariant phenotypic and genomic associations of WT1 mutations in AML were uncovered and rigorously described. Our findings help improving the current understanding and definition of WT1-mutant AML patients' characteristics and clinical outcomes.

Non Random Distribution of Chromosome-21 in Syndromic Cases of Wilms’ Tumors

Wilms’ tumors are the common embryonic childhood solid tumor of kindney and heterogeneous in nature. Karyotypic analysis of Wilms’ tumor has shown a variety of chromosomal aberrations with different (%) frequency of structural and numerical changes in somatic cell. Present study were carried out in eleven cases (n=11) of Wilms’ tumors with different age group (betwen 1.5 year to 10 year). Most striking feature is the involvement of high frequency (>60%) of Wilms’ tumor shows extra copy of chromosome-21 in the karyotypes after using high resolution of GTG banding and FISH analysis. Interestingly, 18% cases of Wilms’ tumor shows loss of Y-chromosome and appearance of (r)Y reporting first time in India. Beside this, short arm of chromosome - 6 and 16 shows two new break points i.e. 6q21.22 and 16q23 might have play an significant role in Wilms’ tumors progression. The other relevant findings were the association of either gain (trisomy) or loss (monosomy) of chromosome with chromatid break points, ring, dicentric or rearrangements of chromosome (translocation) with different frequency. However, this is a rare coincidence that environmental factor (s) might have increase risk of developing Down syndrome (47,XY+21) in Wilms’ tumors, due non - disjunction event and unequal crossing over in cell- division of the disease outcome.

COMPLEX RADIOLOGICAL DIAGNOSIS OF COMPLICATED WILMS' TUMOR

Wilms' tumor is the most common primary malignant renal tumor. It is paradigm for comprehensive treatment of malignant solid tumors in children. Typically, children with this disorder are initially seen with abdominal distention, palpable masses or due to fever of unknown origin. Atypical tumor symptoms can be caused by complications, making it difficult to diagnose the disease. We present three clinical cases of Wilms' tumor in young children. Emergency multidetector computed tomography and magnetic resonance imaging provided the surgeon with sufficient information to perform an urgent radical resection.

A case of Wilms' tumor with spinal cord involvement

Wilms’ tumor is the most common renal tumor of childhood. However, spinal cord involvement has rarely been reported in children with Wilms’ tumor. In this article, we report a 5-year-old boy with Wilms’ tumor who had the unusual presentation of spinal cord involvement. Our purpose is to emphasize that spinal cord involvement may be seen in children with Wilms’ tumor. (J Pediatr Neurol 2003; 1(1): 47-50).

Management of nine cases of Wilms’ tumour with intracardiac extension — a single centre experience

AimThe aim of this study was to review the management of children with Wilms’ tumour who have intracardiac extension. Patients and MethodsData were collected from patient notes regarding presentation, operative details, and outcome. ResultsFrom 1984 through 2011, 264 children with Wilms’ tumour were treated at our hospital. Nine (3.4%) had cavo-atrial extension of the tumour thrombus. The thrombus extended into the right ventricle in two children and involved the hepatic veins in both, and also two others. Pre-operative chemotherapy was administered in eight children with complete regression of the intra-cardiac tumour thrombus in two cases. One child died preoperatively of septicaemia and respiratory failure after two doses of chemotherapy. Six children with intra-cardiac tumour were operated on under cardiopulmonary bypass (CPB) with deep hypothermia and circulatory arrest (DHCA). The mean ischemic time was 30min. There was one peri-operative death in a child with hepatic vein involvement and Budd–Chiari syndrome. All others made a good postoperative recovery. All tumours were favourable histology. To date four children are still alive and disease free. Three children have died as a result of pulmonary metastases. ConclusionIntracardiac extension of Wilms’ tumour is rare, and the management is technically challenging. Pre-operative chemotherapy is effective. CPB and DHCA for excision of the cavo-atrial tumour thrombus may be necessary. Distant metastatic disease is common and determines long term prognosis. Hepatic vein extension complicates surgery and remains challenging.

Morphological Features of Wilms’ Tumour in a Tertiary Health Care Institution: Our Findings

Nephroblastoma or Wilms’ tumour is the most common primary renal malignancy of childhood. Despite being a malignant tumour, a survival rate of over 90% is now seen today (compared to 30% in the thirties) and this resulted from the success of collaborative trials and the use of multimodal therapy. Black children have a 2.5 times increased incidence over their white counterparts and the sex ratio is approximately 1.0. It is also associated with a number of recognised syndromes. The most important prognostic indicators for Wilms’ tumour are the histological subtype and the stage at presentation. Although, studies have been carried out on this tumour focussing on the clinical aspect, it is worthy of note that very little study has been done on the morphological features of this tumour in this centre and the country at large. The purpose of this study is therefore to look at the morphological patterns of Wilms’ tumour seen in this centre and if possible determine whether a relationship exists between the size, position of the tumour and the histological subtype, and finally, if a particular histological subtype is age-related. Patients and method: This is a retrospective study of the cases of Wilms’ tumour seen in the division of paediatric surgery in our tertiary health care institution over a 5-year period i.e. (from Jan 2008 to Dec 2012). The nephrectomy samples of these patients were sent to the department of pathology and forensic medicine in the same institution. During grossing of the samples, adequate attention was paid to any obvious degenerative changes such as haemorrhage and necrosis. Where these changes were seen, they were recorded. The tumour sizes in the largest diameter and weights were also recorded. This was followed by histopathological reports which not only included the diagnosis, but also the histological types. These were all recorded in a pre-designed data form. The age at presentation in months and sex were also recorded in the form. All these were analysed using the statistical package for social science (SPSS) Software version 17. Results: In this study, 44 patients had Wilms’ tumour with males representing 26 (59.1%) while females accounted for 18 (40.9%) and a male to female ratio was 1.4:1. The ages of the patients ranged from 10 months to 8 years with mean age value of 4 ± 2.91. The mode as well as the median age was 3 years. 24 (54.5%) of the tumours were located on the left position while 20 (45.5%) were seen on the right side. Most of the tumours weighed between 501-1000 grams representing (40.9%). In terms of tumour volume, majority measured between 1001-2000 cm3 accounting for (40.9%). Necrosis was observed in 95.5% of the cases. It is also worthy of note that all the tumours had areas of haemorrhage grossly, and 100% exhibiting triphasic histological pattern. This characterizes the classical WT. Bilateral or Synchronous tumour was not seen in this study. Conclusion: The predominant histological pattern of Wilms’ tumour in this centre is the triphasic pattern representing the classical wilm’s tumour. It is most common in children between the ages of 1 and 5 years with average tumour weight of between 501 and 1000 gm. The bilateral (synchronous) or metachronous type of Wilms’ tumour was not seen in this study.

Genetic alterations of WWOX in Wilms’ tumor are involved in its carcinogenesis

Loss of heterozygosity (LOH) in 16q appears in ~20-30% cases of Wilms' tumor. Within this region, known as common fragile site FRA16D, the WWOX tumor suppressor gene is located. Abnormalities of WWOX gene expression levels were observed in many tumor types and were associated with worse prognosis. The purpose of this study was to investigate the role of the WWOX tumor suppressor gene in Wilms' tumor samples. We evaluated the correlation between expression of WWOX and genes involved in proliferation (Ki67), apoptosis (BCL2, BAX), signal transduction (ERBB4, ERBB2, EGFR), cell cycle (CCNE1, CCND1), cell adhesion (CDH1) and transcription (TP73) using real-time RT-PCR in 23 tumor samples. We also analyzed the potential causes of WWOX gene expression reduction i.e., promoter methylation status (MethylScreen method) and loss of heterozygosity (LOH) status. We revealed a positive correlation between WWOX expression and BCL2, BCL2/BAX ratio, EGFR, ERBB4 isoform JM-a, TP73 and negative correlation with both cyclins. Loss of heterozygosity of the WWOX gene was observed only at intron 8, however, it had no influence on the reduction of its expression levels. Contrary to LOH, methylation of the region covering the 3' end of the promoter and part of exon 1 was associated with statistically significant reduction of WWOX gene expression levels. In the present study we reveal that in Wilms' tumors the WWOX expression levels are positively associated with the process of apoptosis, signal transduction through the ErbB4 pathway and EGFR and negatively with the regulation of the cell cycle (by cyclin E1 and D1). Moreover, our analysis indicates that in this type of tumor the expression of the WWOX gene can be regulated by an epigenetic mechanism--its promoter methylation.

Recurrent pulmonary tumoral embolism and sudden death as the presenting symptom of Wilms' tumor

Only 4-6% of children with renal tumor show inferior vena caval or right atrial infiltration at presentation. Tumor emboli are even rarer, and so far, sudden death as the presenting symptom has only been described at presentation in Wilms' tumor in eight cases. We report a unique case of Wilms' tumor that presented with small pulmonary emboli and immediately after as that was diagnosed before death by detection of small emboli and immediately after sudden death as massive pulmonary embolism. It seems that in cases of invasive vascular infiltration with a stable hemodynamic condition at diagnosis immediate surgery may be necessary.

Germline Bone Morphogenesis Protein Receptor 1A Mutation Causes Colorectal Tumorigenesis in Hereditary Mixed Polyposis Syndrome

Hereditary mixed polyposis syndrome (HMPS) is characterized by polyps of mixed adenomatous/hyperplastic/atypical juvenile histology that are autosomal dominantly inherited and that eventually lead to colorectal cancer (CRC). Although CRC with adenomatous polyps is initiated by inactivating adenomatous polyposis coli (APC), the initiating event of CRC with mixed polyps remains unclear. We aimed to identify the underlying germline defect in HMPS. We screened for bone morphogenesis protein receptor 1A (BMPR1A) mutation by exonic sequencing, reverse-transcriptase polymerase chain reaction (PCR) followed by cDNA sequencing, and multiplex ligation-dependent probe amplification (MLPA) analysis in eight Singapore Chinese HMPS families. Germline BMPR1A defects were found in four (50%) families. In two families, it is shown to co-segregate with the disease phenotype in all affected members over three generations, indicating that it is the disease-causing mutation. CRC incidence is 75%. The most defining characteristic is the presence of mixed hyperplastic-adenomatous polyps. Juvenile polyps are rarely reported, and if present, are usually of mixed components. Detailed histology of the polyps from one patient over 11 years distinguishes HMPS from juvenile polyposis syndrome (JPS). We report further the first cases of Wilms' tumor and papillary thyroid carcinoma associated with BMPR1A germline defect. Germline BMPR1A defect is the disease-causing mutation in 50% of the HMPS families. If patients present with mixed morphology polyps in the large bowel that are autosomal dominantly inherited and corresponding absence of upper gastrointestinal abnormalities, the gene to begin mutation screening should be BMPR1A rather than APC.

Adult Wilms’ tumor masquerading as pyonephrosis: a diagnostic dilemma

In the era of modern imaging, modalities like ultrasonography, computed tomography and magnetic resonance imaging diagnosis of renal mass lesions has become more accurate. Nevertheless, rare cases of renal adenocarcinoma and other primary renal tumors have been rarely reported to mimic pyonephrosis, renal abscess, perinephric abscess or tuberculosis. We report, for the first time in literature, a case of Wilms' tumor mimicking as a case of pyonephrosis. The incidence, possible causes and implications of such a misdiagnosis and the measures to avoid the same are discussed.

Wilms' tumor, pancreatic islet cell carcinoma, and pheochromocytoma in a child

We present the first case of Wilms' tumor, pancreatic islet cell carcinoma, and pheochromocytoma affecting the same individual. This case underscores the importance of repeat biopsies in patients with multiple neoplasms to confirm the diagnosis and guide management.

Effect of preoperative transcatheter arterial chemo-embolization on activity of cell proliferation in Wilms; tumor

To investigate the effect of preoperative transcatherter arterial chemo-embolization (TACE) on the cell proliferation in Wilms; tumor. Forty-one cases of Wilms; tumor diagnosed by histopathology were divided into two groups: in TACE group, 23 patients received TACE first and were operated 2 weeks later; in control group, 18 patients were operated alone. A comparative analysis of the pathological finding was made in two groups, and the expression of PCNA and VEGF in tumor tissue was detected by immunohistochemistry. The degeneration of tumor tissue such as tumor cell necrotic, broken, disappearance occurred in 17 cases of TACE group and in 4 cases of control group, respectively (P <0.01). The expression of PCNA in TACE group and in control group was 1/23 (4.3 %) and 9/18(50.0 %), respectively (P <0.01). VEGF was expressed in 7/23 (30.4 %) of TACE group and 9/18 (50.0 %) of control group (P=0.283). TACE can significantly inhibit proliferation and enhance degeneration of Wilms; tumor cells.

IMMUNOHISTOCHEMICAL ANALYSIS OF GAMMA CATENIN IN WILMS' TUMORS

The aim of our study was to investigate the expression of γ-catenin in normal kidney and in Wilms' tumor by immunohistochemistry and to correlate the results with tumor stage, histological type, and prognostic group. We investigated 28 cases of Wilms' tumor, 2 Wilms' tumor metastases in lungs, and 1 specimen of normal renal tissue. Expression of γ-catenin was detected in 14 cases. There was a weak inverse relationship between γ-catenin expression and tumor stage. Expression of γ-catenin was detected in various histologic types of Wilms' tumor, but there was no statistically significant correlation, except in cases with diffuse anaplasia that were negative. In 2 metastatic cases and in the case of bilateral Wilms' tumor γ-catenin immunostaining was not observed Our findings suggest an absence of strong correlation between the loss of γ-catenin and unfavorable outcome.

A comparative study of intratumoral chemotherapy in advanced childhood common solid tumors.

Background:Advanced and inoperable solid tumors in children are great killer despite aggressive multimodality treatment. Intravenous chemotherapy, due to high dose of drug given systemically, at times leads to abandonment of therapy due to systemic toxicities. To overcome this problem lots of studies are going on to explore alternative modes of giving anticancer drugs so as to decrease the systemic toxicities of the drugs and increase their therapeutic index at the same time.Aim:The study was conducted to know the results of anterior intratumoral chemotherapy and its comparison to anterior intravenous chemotherapy.Materials and Methods:Forty patients of advanced inoperable solid tumors in children (Wilms' tumor and neuroblastoma) between 2000-2004 were randomly allocated to two groups. Group A (20 patients) was given intratumoral chemotherapy while Group B (20 patients) was given intravenous chemotherapy. Both the groups were compared in terms of reduction in size and volume, resectability of tumor, histopathological changes and side-effects of chemotherapeutic drugs. The Institute's ethics committee approved this study.Results:Males were predominant in both type of cases (Wilms' tumor and neuroblastoma) in both the groups (Group A and Group B). Mean age in the study was 3.27 years. All cases in Group A had Stage III disease except three cases which had Stage IV disease (one case of Wilms' tumor and two cases of neuroblastoma) while in Group B only two cases had Stage IV disease (one case of Wilms' tumor and one case of neuroblastoma). Intratumoral chemotherapy was found to be superior over intravenous chemotherapy in terms of reduction of size and volume (63% in Group A vs. 22% in Group B). The resectability was 70% in the intratumoral group in comparison to 40% in the intravenous group. The overall good histopathological response was 71% in Group A as opposed to 0% in Group B. Moreover, the incidence and severity of side-effects of chemotherapy and morbidity was less in intratumoral chemotherapy. Mortality was also low in Group A (5%) in comparison to Group B (20%).Conclusion:In this study intratumoral chemotherapy was found to be superior over intravenous chemotherapy in terms of better and early tumor regression, minimal side-effects, better tumor resectability and well response on histopathological criteria. This study is still going on at our center where different drug combinations, different drug doses, their toxicities, their mechanisms of action, their serum levels and long-term results of intratumoral mode of chemotherapy are to be evaluated thoroughly in future.

Prophylactic bilateral salpingo-oopherectomy in a 17-year-old with Frasier syndrome reveals gonadoblastoma and seminoma: a case report

Mutations in the Wilms' tumor gene are present in children with Frasier syndrome, Denys-Drash syndrome, WAGR syndrome, and some cases of Wilms' tumor. The Wilms' tumor gene product, WT1, is necessary for normal urogenital development. Frasier syndrome is an association between focal segmental glomerulosclerosis, beginning in the second and third decade, male to female sex reversal, and dysgenetic gonads. We report a case of Frasier syndrome in a 17-year-old adolescent girl with renal failure, kidney transplant, and dysgenetic gonads, with development of gonadoblastoma and dysgerminoma (seminoma). The diagnosis of Frasier syndrome was based on nephrotic syndrome with diffuse mesangial sclerosis leading to chronic renal failure, dysgenetic gonads, 46 XY karyotype in a phenotypic female, and a mutation in the Wilms' tumor gene. Prophylactic laparoscopic bilateral salpingo-oopherectomy revealed gonadoblastoma and seminoma in opposite atrophic ovaries as well as a hypoplastic uterus. Early prophylactic resection of dysgenetic gonads is indicated in children with Frasier syndrome to prevent the development of germ cell malignancy.

Primary Malignant Renal Tumors in Infancy and Childhood: CT Appearances

Objective: To investigate the imaging manifestation of primary malignant renal tumor with CT. Methods: Forty-three cases of surgically and pathologically confirmed primary malignant renal tumor were retrospectively reviewed. Un-contrast and contrast CT was performed in all 43 patients in which 15 patients received MRI examination. Results: The residual normal renal tissue of 29 cases out of 34 cases of Wilms' tumor was enhanced and manifested "crescent sign" or "ring sign". Four cases of malignant rabdoid tumor (RTK) manifested as large mass with notable necrosis and subcapsular fluid collection; Two cases of clear cell sarcoma (CCS) showed metastases to the skull which could indicate the diagnosis; Renal cell carcinoma (RCC) (n=3) showed calcification in 1 case. Conclusion: CT can precisely delineate the location, size, extent of involvement, imaging characteristics and metastases of renal tumor, which can provide information necessary to the clinical staging, therapy planning and prognosis of the tumors.

Retrospective Analysis of Twenty-Six Cases of Wilms' Tumour for Factors Predicting Metastasis and Relapse

Retrospective Analysis of Twenty-Six Cases of Wilms' Tumour for Factors Predicting Metastasis and Relapse

Wilms’ tumor and exposures to residential and occupational hazardous chemicals

This case-control study examines the association between residential and occupational exposures to hazardous chemicals and the risk of Wilms’ tumor. The study included 303 cases recruited from six state cancer registries, who were diagnosed between January 1, 1992 and December 31, 1995. A total of 575 controls selected through random digit dialing were frequency matched to the cases. A standard questionnaire was administered to participants during a telephone interview. Parental residential addresses and locations of US Environmental Protection Agency National Priority List (NPL) sites were geocoded and analyzed, along with occupational exposure information. There were no cases of Wilms’ tumor found in individuals living within one-half mile distance of a hazardous waste site. However, elevated odds ratios were found for using hairdressing chemicals, motor oil, paint, paint stripper, and pesticides during the pregnancy term and during the 2-year period prior to birth. The findings do not support the hypothesis that Wilms’ tumor is associated with residing near an NPL site.

Risk of Wilms’ tumour with multicystic kidney disease: a systematic review

Background: Children with multicystic kidney disease (MCKD) are increasingly managed conservatively and are followed up throughout childhood because they are perceived to be at increased risk of developing Wilms’ tumour....