Systematic Review and Meta-analysis of Laparoscopic Versus Open Radical Nephrectomy for Paediatric Renal Tumors With Focus on Wilms' Tumor.

OBJECTIVE: To summarize and evaluate the outcomes of laparoscopic radical nephrectomy (LRN) and compare its safety and efficacy with open radical nephrectomy (ORN) in pediatric renal tumors (RT) and Wilms' tumors (WT). BACKGROUND: ORN is the gold standard treatment for pediatric RT, consisting predominantly of WT. LRN is gaining popularity but remains controversial in pediatric surgical oncology. METHODS: A systematic search was performed for all eligible studies on LRN and comparative studies between LRN and ORN in pediatric RT and WT. Meta-analysis, subgroup analysis, and sensitivity analysis were conducted. The main endpoints were cancer-related outcomes and surgical morbidity. Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed. RESULTS: No levels I to II studies were identified. LRN was feasible in nearly 1 in 5 pediatric RT and WT after neoadjuvant chemotherapy, with pooled mid-term oncological outcomes (<7% local recurrence, >90% event-free survival) comparable with those of ORN. There was no strong evidence of an increased risk of intraoperative tumor spillage, but lymph node harvest was inadequate in LRN. Large tumors crossing the ipsilateral spinal border were associated with a trend for intraoperative complications and positive margins. Pooled complications rate and hospital stay duration were similar between LRN and ORN. Long-term (>3 years) outcomes are unknown. CONCLUSIONS: Available level III evidence indicates that LRN is a safe alternative to ORN for carefully selected cases, with similar spillage rates and mid-term oncological outcomes. However, there was no advantage in surgical morbidity and lymph node harvest was inadequate with LRN. Tumor-matched-group studies with long-term follow-up are required. LEVEL OF EVIDENCE: Level III.

Metachronous Wilms Tumor, Glioblastoma, and T-cell Leukemia in an Child With Constitutional Mismatch Repair Deficiency syndrome due to Novel Mutation in MSH6 (c.2590G>T).

Constitutional mismatch repair deficiency (CMMRD) is an autosomal recessively inherited childhood cancer predisposition syndrome results from biallelic germline mutations affecting the key DNA mismatch repair gene: MLH1, MSH2, MSH6, or PMS2. CMMRD is associated with a high risk of developing early onset of central nervous system tumors, hematologic, and intestinal tract tumors. Clinical manifestations, genetic screening, and cancer prevention strategies are limited. In this report we present a patient with metachronous Wilms tumor, glioblastoma, and acute T-cell lymphoblastic leukemia. He had cutaneous features of neurofibromatosis type 1 (NF1). Molecular testing revealed a novel homozygous mutation in MSH6 (c.2590G>T; p.G864*) that has not been reported previously. CMMRD should be considered in patients with cutaneous features similar to NF1 if tumor is found other than expected tumors in NF, early onset cancer, and strong family history of cancer.

METTL3 polymorphisms and Wilms tumor susceptibility in Chinese children: A five-center case-control study.

BACKGROUND: Wilms tumor is a common pediatric tumor worldwide. Methyltransferase like 3 (METTL3) is a core gene of the N6 -methyladenosine (m6 A) modification that widely affects the transcription of tumor-related genes in eukaryotes. METTL3 has been extensively investigated in various tumors but not Wilms tumor. METHODS: We describe a five-center case-control study with 414 patients and 1199 controls aiming to explore the associations between METTL3 polymorphisms (rs1061026 T>G, rs1061027 C>A, rs1139130 A>G and rs1263801 G>C) and Wilms tumor susceptibility. A TaqMan real-time polymerase chain reaction was performed for genotyping. Odds ratios (ORs) and 95% confidence intervals (CIs) were reported as evaluation indicators to determine any associations. RESULTS: Referring to the preliminary analysis results, protective genotypes were identified as rs1061026 TG/GG, rs1061027 CA/AA, rs1139130 GG and rs1263801 GC/CC. The children with three protective genotypes were less likely to develop Wilms tumor than children without protective genotypes (adjusted OR = 0.68, 95% CI = 0.46-0.999, p = 0.0496). Similarly, stratified analysis of the subgroup aged > 18 months, carrying 3 or 4 protective genotypes, was a protective factor for Wilms tumor compared to carrying 0-2 protective genotypes (adjusted OR = 0.59 95% CI = 0.39-0.91, p = 0.016). However, we did not observe any other significant results. CONCLUSIONS: The combined effect of METTL3 polymorphisms reduce Wilms tumor susceptibility in Chinese children. This conclusion requires further verification.

CD8+ T-cell lymphocytes infiltration predict clinical outcomes in Wilms' tumor.

The abundance and location of CD8+ tumor-infiltrating lymphocytes demonstrate important facets of the anticancer immune response. CD8-expressing lymphocytes have been used in immunotherapy for multiple cancers. This study aims to determine the association between the abundance and localization of CD8+ tumor-infiltrating lymphocytes and clinical outcomes of Wilms' tumor. This retrospective study employed 42 pediatric patients diagnosed with Wilms' tumor. CD8+ tumor-infiltrating lymphocyte counts were calculated based on the mean percentage of stroma occupied by CD8+ lymphocytes at the center and the invasive border of the tumor using immunohistochemistry. CD8+ tumor-infiltrating lymphocyte counts were significantly higher in the center and the invasive border of the early-stage tumor samples. CD8+ tumor-infiltrating lymphocytes in the invasive border and tumor center positively correlated with tumor invasion, regional lymph node invasion, histological type, metastasis, and stage of the tumor. A high CD8+ tumor-infiltrating lymphocyte scores at the invasive margin of the tumor correlated with low tumor recurrence. Low CD8+ tumor-infiltrating lymphocyte scores in the two tumor regions correlated with poor prognosis and shorter disease-free survival. Overall, these findings show that patients with high CD8+ tumor-infiltrating lymphocytes are associated with better clinical outcomes. Therefore, measuring the abundance of CD8+ tumor-infiltrating lymphocytes may be useful in predicting response to cancer immunotherapies.

Phenotype evolution and health issues of adults with Beckwith-Wiedemann syndrome.

BACKGROUND: Beckwith-Wiedemann syndrome (BWS) phenotype usually mitigates with age and data on adulthood are limited. Our study aims at reporting phenotype evolution and health issues in adulthood. METHODS: 34 patients (16 males), aged 18-58 years (mean 28.5) with BWS were enrolled. RESULTS: 26 patients were molecularly confirmed, 5 tested negative, and 3 were not tested. Final tall stature was present in 44%. Four patients developed Wilms' Tumor (2, 3, 5, and 10 years, respectively); one hepatoblastoma (22 years); one acute lymphoblastic leukemia (21 years); one adrenal adenoma and testicular Sertoli cell tumor (22 and 24 years, respectively); and three benign tumors (hepatic haemangioma, uterine myoma, and mammary fibroepithelioma). Surgery for BWS-related features was required in 85%. Despite surgical correction several patients presented morbidity and sequelae of BWS pediatric issues: pronunciation/swallow difficulties (n = 9) due to macroglossia, painful scoliosis (n = 4) consistent with lateralized overgrowth, recurrent urolithiasis (n = 4), azoospermia (n = 4) likely consequent to cryptorchidism, severe intellectual disability (n = 2) likely related to neonatal asphyxia and diabetes mellitus (n = 1) due to subtotal pancreatectomy for intractable hyperinsulinism. Four patients (two males) had healthy children (three physiologically conceived and one through assisted reproductive technology). CONCLUSIONS: Adult health conditions in BWS are mostly consequent to pediatric issues, underlying the preventive role of follow-up strategies in childhood. Malignancy rate observed in early adulthood in this small cohort matches that observed in the first decade of life, cumulatively raising tumor rate in BWS to 20% during the observation period. Further studies are warranted in this direction.

A role for the Perlman syndrome exonuclease Dis3l2 in the Lin28-let-7 pathway.

The pluripotency factor Lin28 blocks the expression of let-7 microRNAs in undifferentiated cells during development, and functions as an oncogene in a subset of cancers. Lin28 binds to let-7 precursor (pre-let-7) RNAs and recruits 3' terminal uridylyl transferases to selectively inhibit let-7 biogenesis. Uridylated pre-let-7 is refractory to processing by Dicer, and is rapidly degraded by an unknown RNase. Here we identify Dis3l2 as the 3'-5' exonuclease responsible for the decay of uridylated pre-let-7 in mouse embryonic stem cells. Biochemical reconstitution assays show that 3' oligouridylation stimulates Dis3l2 activity in vitro, and knockdown of Dis3l2 in mouse embryonic stem cells leads to the stabilization of pre-let-7. Our study establishes 3' oligouridylation as an RNA decay signal for Dis3l2, and identifies the first physiological RNA substrate of this new exonuclease, which is mutated in the Perlman syndrome of fetal overgrowth and causes a predisposition to Wilms' tumour development.

Nephroblastoma in bester sturgeon, a cultured hybrid of Huso huso × Acipenser ruthenus: Diagnostic imaging, clinical and histopathological study.

Abdominal distention occurred at an incidence of 1% (15 from 1500 fish) in the population of 1-year-old bester (Huso huso × Acipenser ruthenus). Computed tomography (CT) images and radiographs showed a soft tissue mass compressed the posterior part of the swim bladder. Ultrasonography showed that the masses had different patterns. Internal examination revealed the abdominal cavities to be filled with large masses which appeared to encompass most of the visceral organs, including the swim bladder. The masses originated from the posterior kidney. Histologically, the masses were composed of mixtures of embryonal epithelial (tubules and glomeruli), blastema and mesenchymal tissues. The tubules showed cystic, papillary and tubular patterns. Tubules and glomeruloid structures were surrounded by proliferating blastema cells. The primitive mesenchyme was composed of loose streams and whorls of spindle to stellate cells with elongate nuclei. Histological findings in the skeletal muscles, hypoderm and spleen confirmed the metastatic tumour from the kidney in two cases. Immunohistochemically, neoplastic cells of the tubules and glomeruloid structures were positive for cytokeratin AE1/AE3. Sections stained with Masson's trichrome showed blue staining of the stroma. The histopathologic findings were consistent with nephroblastoma.

Index analysis and human health risk model application for evaluating ambient air-heavy metal contamination in Chemical Valley Sarnia.

The impacts of air emissions as a consequence of industrial activities around communities of human habitation have been extensively reported. This study is the first to assess potential adverse human health effects in the Chemical Valley Sarnia (CVS) area, around the St. Clair River, using health risk models, ecological and pollution indices. Large quantities of particulate matters (PM) are generated from anthropogenic activities, which contain several heavy metals in trace quantities with potentially adverse effects to humans and environmental health. The distribution, and human health impact assessment of trace element concentrations in PM fractions were examined. Elemental concentrations of As, Cd, Cr (VI), Cu, Fe, Mn, Pb, Ni, Zn were determined in the PM size-segregated samples collected from the CVS area between 2014 and 2017. The results showed relatively high concentration of PM<2.5 (87.19±8.1(mgm3)) which is approximately 4 times the WHO air quality guidelines. Pb concentration (143.03 ± 46.87ηg/m3) was 3.6 times higher than the air quality standards of NAAQS. Cr (VI) showed moderate to considerable contamination ( Cf=4) in the CVS while Cr (VI), Pb, and Ni had enrichment factor Ef < 3 (minimal), signifying contributions from anthropogenic activities. Pollution load index (PLi) value observed was 1.4 indicating human health risk from the PM, especially for the children in the area. The deposition fluxes (DΦ) showed that PM-bound metals could potentially bypass the head airways and cause damages to the tracheobronchial tree, increasing the human health risks of nephroblastomasis development. The main route of entry for the heavy metal bound PM in humans were observed as through ingestion and inhalation. The highest total excess cancer risks observed for children (6.7×10-4) and adult (1.0×10-4) indicating potential cancer effects. The Incremental Lifetime Cancer Risk (ILCR) increased from Pb < Ni < Cd < Cr (VI) < As. Overall, children are more likely to develop carcinogenic and non-carcinogenic health effects from exposures to elemental concentrations of airborne PM in the study area.

Bilateral Wilms tumour: a review of clinical and molecular features.

Wilms tumour (WT) is the most common paediatric kidney cancer and affects approximately one in 10 000 children. The tumour is associated with undifferentiated embryonic lesions called nephrogenic rests (NRs) or, when diffuse, nephroblastomatosis. WT or NRs can occur in both kidneys, termed bilateral disease, found in only 5-8% of cases. Management of bilateral WT presents a major clinical challenge in terms of maximising survival, preserving renal function and understanding underlying genetic risk. In this review, we compile clinical data from 545 published cases of bilateral WT and discuss recent progress in understanding the molecular basis of bilateral WT and its associated precursor NRs in the context of the latest radiological, surgical and epidemiological features.

Effects of malnutrition on treatment-related morbidity and survival of children with cancer in Nicaragua.

BACKGROUND: Most children with cancer live in resource-limited countries where malnutrition is often prevalent. We identified the relationship between malnutrition and treatment-related morbidity (TRM), abandonment of therapy, and survival of children with cancer in Nicaragua to better inform targeted nutritional interventions. PROCEDURE: We conducted a retrospective review of patients aged 6 months to 18 years with newly diagnosed acute lymphoblastic leukemia, acute myeloid leukemia (AML), Wilms tumor, Hodgkin lymphoma, or Burkitt lymphoma (BL) who were treated between January 1, 2004, and December 31, 2007 at Children's Hospital Manuel de Jesus Rivera in Managua, Nicaragua. Statistical analysis examined the relations among nutritional status and cancer type, risk category, TRM, and event-free survival (EFS). RESULTS: Sixty-seven percent of patients (189/282) were malnourished at diagnosis. Malnutrition was highest among patients with Wilms tumor (85.7%), BL (75%), and AML (74.3%). A total of 92.2% of patients (225/244) experienced morbidity during the first 90 days. Malnutrition was associated with severe infection (P = 0.033). Severely malnourished patients had ≥grade 3 TRM on more days (P = 0.023) and were more likely to experience severe TRM on >50% of days (P = 0.032; OR, 3.27 [95% CI, 1.05-10.16]). Malnourished patients had inferior median EFS (2.25 vs. 5.58 years; P = 0.049), and abandoned therapy more frequently (P = 0.015). CONCLUSIONS: In Nicaragua, pediatric oncology patients with malnutrition at diagnosis experienced increased TRM, abandoned therapy more frequently, and had inferior EFS. Standardized nutritional evaluation of patients with newly diagnosed cancer and targeted provision of nutritional support are essential to decrease TRM and improve outcomes.

Gastrointestinal Findings in the Largest Series of Patients With Hereditary Biallelic Mismatch Repair Deficiency Syndrome: Report from the International Consortium.

OBJECTIVES: Hereditary biallelic mismatch repair deficiency (BMMRD) is caused by biallelic mutations in the mismatch repair (MMR) genes and manifests features of neurofibromatosis type 1, gastrointestinal (GI) polyposis, and GI, brain, and hematological cancers. This is the first study to characterize the GI phenotype in BMMRD using both retrospective and prospective surveillance data. METHODS: The International BMMRD Consortium was created to collect information on BMMRD families referred from around the world. All patients had germline biallelic MMR mutations or lack of MMR protein staining in normal and tumor tissue. GI screening data were obtained through medical records with annual updates. RESULTS: Thirty-five individuals from seven countries were identified with BMMRD. GI data were available on 24 of 33 individuals (73%) of screening age, totaling 53 person-years. The youngest age of colonic adenomas was 7, and small bowel adenoma was 11. Eight patients had 19 colorectal adenocarcinomas (CRC; median age 16.7 years, range 8-25), and 11 of 18 (61%) CRC were distal to the splenic flexure. Eleven patients had 15 colorectal surgeries (median 14 years, range 9-25). Four patients had five small bowel adenocarcinomas (SBC; median 18 years, range 11-33). Two CRC and two SBC were detected during surveillance within 6-11 months and 9-16 months, respectively, of last consecutive endoscopy. No patient undergoing surveillance died of a GI malignancy. Familial clustering of GI cancer was observed. CONCLUSIONS: The prevalence and penetrance of GI neoplasia in children with BMMRD is high, with rapid development of carcinoma. Colorectal and small bowel surveillance should commence at ages 3-5 and 8 years, respectively.

Phenotype, cancer risk, and surveillance in Beckwith-Wiedemann syndrome depending on molecular genetic subgroups.

Patients with Beckwith-Wiedemann syndrome (BWS) have an increased risk to develop cancer in childhood, especially Wilms tumor and hepatoblastoma. The risk varies depending on the cause of BWS. We obtained clinical and molecular data in our cohort of children with BWS, including tumor occurrences, and correlated phenotype and genotype. We obtained similar data from larger cohorts reported in the literature. Phenotype, genotype and tumor occurrence were available in 229 of our own patients. Minor differences in phenotype existed depending on genotype/epigenotype, similar to earlier studies. By adding patients from the literature, we obtained data on genotype and tumor occurrence of in total 1,971 BWS patients. Tumor risks were highest in the IC1 (H19/IGF2:IG-DMR) hypermethylation subgroup (28%) and pUPD subgroup (16%) and were lower in the KCNQ1OT1:TSS-DMR (IC2) subgroup (2.6%), CDKN1C (6.9%) subgroup, and the group in whom no molecular defect was detectable (6.7%). Wilms tumors (median age 24 months) were frequent in the IC1 (24%) and pUPD (7.9%) subgroups. Hepatoblastoma occurred mostly in the pUPD (3.5%) and IC2 (0.7%) subgroups, never in the IC1 and CDKN1C subgroups, and always before 30 months of age. In the CDKN1C subgroup 2.8% of patients developed neuroblastoma. We conclude tumor risks in BWS differ markedly depending on molecular background. We propose a differentiated surveillance protocol, based on tumor risks in the various molecular subgroups causing BWS. © 2016 Wiley Periodicals, Inc.

A recessive syndrome of intellectual disability, moderate overgrowth, and renal dysplasia predisposing to Wilms tumor is caused by a mutation in FIBP gene.

Clinical classification of overgrowth syndromes represents a challenge since a wide spectrum of disorders result in marked overgrowth. Therefore, there is a continuous effort to identify the genetic basis of these disorders that will eventually facilitate their molecular classification. Here, we have identified the genetic etiology and the pathogenetic mechanism underlying a rare autosomal recessive overgrowth syndrome in three affected siblings. The overgrowth phenotype in the patients was accompanied by developmental delay, learning disabilities, and variable congenital abnormalities. To elucidate the genetic etiology of the disorder, whole-genome genotyping and whole-exome sequencing were used. The disease was mapped to 3p21.1-p14.2 and 11q13.1-q13.4, where an in-frame insertion (c.175_176insTAA) in FIBP gene was revealed. The resulting indel (p.H59LN) was predicted to change the protein conformation with likely deleterious effect on its function as one of the fibroblast growth factor signaling mediators. In vitro cellular proliferation assay and in situ hypridization in vivo were then performed to understand the pathophysiology of the disease. The patients' skin fibroblasts showed an increased proliferation capacity compared to the controls' explaining the observed overgrowth phenotype. In addition, we detected Fibp expression most notably in the brains of mice embryos suggesting a possible effect on cognitive functions early in development. To date, only one patient has been reported with a homozygous nonsense mutation in FIBP exhibiting an overgrowth syndrome with multiple congenital abnormalities. Taken all together, these findings provide convincing evidence implicating FIBP aberrations in the newly recognized overgrowth syndrome and expand the associated phenotypes to include possible Wilms tumor predisposition. © 2016 Wiley Periodicals, Inc.

Association of TP53 polymorphisms on the risk of Wilms tumor.

BACKGROUND: Molecular factors influencing Wilms tumor (WT) development remain largely unknown. TP53 mutations seem to be restricted to the anaplastic WT subtype. However, TP53 polymorphisms do not have a defined role in the disease. PROCEDURE: To assess the impact of TP53 mutations and polymorphisms (PIN2, PIN3, and PEX4) on risk of development, age at diagnosis, and survival in WT, we analyzed 46 blood DNA samples and 31 fresh tumor DNA samples from 52 patients with WT. Sequencing of TP53 exons 2-11 was performed. RESULTS: Tumor DNA analysis revealed TP53 pathogenic missense mutations (p.V197M, p.R213Q, p.R248W, and p.R337C) in four samples (12.9%). Blood DNA samples revealed a novel intronic mutation, IVS2 + 37C > T, in one patient (2.2%). Bilaterality was associated with a twofold decrease in survival (P = 0.00037). Diffuse anaplasia also presented a lower survival probability compared to patients with non-anaplastic tumors, or with focal anaplasia (P = 0.045). Patients with a TP53 somatic mutation showed survival probability of 37.5% versus 85.0% for patients with no somatic mutations, although the difference was not statistically significant (P = 0.0706). PIN3 duplicated allele was associated with a 20-month later mean age at diagnosis (P = 0.0084). TP53 PEX4 C allele showed an increased risk for WT development (P = 0.0379). No relationship was found between survival and gender, age at diagnosis, or the less frequent alleles of PIN2, PIN3, and PEX4. CONCLUSIONS: Our results demonstrate an association between PIN3 and age at diagnosis, as well as an association of PEX4 and risk of development of WT.

Perinatal risk factors for Wilms tumor in a Swedish national cohort.

Perinatal risk factors including high birth weight have been associated with Wilms tumor in case-control studies. However, these findings have seldom been examined in large cohort studies, and the specific contributions of gestational age at birth and fetal growth remain unknown. We conducted the largest population-based cohort study to date consisting of 3,571,574 persons born in Sweden in 1973-2008, followed up for Wilms tumor incidence through 2009 to examine perinatal risk factors. There were 443 Wilms tumor cases identified in 66.3 million person-years of follow-up. After adjusting for gestational age and other perinatal factors, high fetal growth was associated with increased risk of Wilms tumor among girls (hazard ratio per 1 standard deviation (SD), 1.36; 95% CI 1.20-1.54; P < 0.001), but not boys (1.10; 95% CI 0.97-1.25; P = 0.14) (P interaction = 0.02). Among girls, high fetal growth was associated with disease onset before age 5 years (odds ratio per 1 SD, 1.47; 95% CI 1.28-1.69; P < 0.001), but not beyond (1.00; 95% CI 0.76-1.31; P = 0.99). No clear associations were found for gestational age at birth or other perinatal factors. In this large cohort study, high fetal growth was associated with Wilms tumor before age 5 years among girls. These findings suggest that early-life growth factor pathways for Wilms tumor may be more common among girls than boys. Further elucidation of these mechanisms may reveal better targets for prevention or treatment of specific subtypes of Wilms tumor.

Results of fifteen-year follow-up from a single center: findings and risks for tumor development in isolated hemihyperplasia cases.

Isolated hemihyperplasia is abnormal asymmetric growth of one or more parts of the body without any underlying disease. The risk for the development of embryonal tumor is increased in the subjects with isolated hemihyperplasia. The study presented here retrospectively evaluated the clinical data and the risk for tumor development in the cases with isolated hemihyperplasia. 24 cases with isolated hemihyperplasia were retrospectively evaluated. An extremity segment has been involved in 16.7%, an extremity has been entirely involved in 37.5%, more than one extremity have been involved on the same side in 16.7%, and definitely half of the body including the face has been involved in 25% of the patients, whereas one side of the face has been involved in only one case. Wilms tumor in the left abdomen (4.2%) was developed in one case. Isolated hemihyperplasia is a rare clinical picture that enhances the risk for the development of embryonal tumors.

Nephrogenic remnants: occasional ultrasound diagnosis and follow-up.

Nephrogenic remnants (NRs) are nodular collections of undifferentiated renal blastema cells in the postnatal kidney that are recognized as putative precursor lesions of Wilms tumor (WT). NRs may remain stationary, undergo regression, or proliferate. In the last case, there is a high risk for the development of a WT. During infancy, they are most frequently of microscopic size, to be found only at autopsy in approximately 1% of infant kidneys. Approximately 1 out of 100 microscopic lesions persist and grow developing lesions large enough to be seen by ultrasound in the first months of life. We report on a case of NRs in a six year old child, as incidental finding during abdominal ultrasound performed for other purposes. In consideration of the potential evolution in WT, after a period of close surveillance of 14 months, the lesion was resected. Histological examination revealed the presence of NRs, no neoplastic lesions were found. Currently the patient is 16 years old, in good health, and there have been no signs of recurrence.

Multiple tumor types including leiomyoma and Wilms tumor in a patient with Gorlin syndrome due to 9q22.3 microdeletion encompassing the PTCH1 and FANC-C loci.

Gorlin syndrome or nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant condition mainly characterized by the development of mandibular keratocysts which often have their onset during the second decade of life and/or multiple basal cell carcinoma (BCC) normally arising during the third decade. Cardiac and ovarian fibromas can be found. Patients with NBCCS develop the childhood brain malignancy medulloblastoma (now often called primitive neuro-ectodermal tumor [PNET]) in 5% of cases. The risk of other malignant neoplasms is not clearly increased, although lymphoma and meningioma can occur in this condition. Wilms tumor has been mentioned in the literature four times. We describe a patient with a 10.9 Mb 9q22.3 deletion spanning 9q22.2 through 9q31.1 that includes the entire codifying sequence of the gene PTCH1, with Wilms tumor, multiple neoplasms (lung, liver, mesenteric, gastric and renal leiomyomas, lung typical carcinoid tumor, adenomatoid tumor of the pleura) and a severe clinical presentation. We propose including leiomyomas among minor criteria of the NBCCS.

Lateralized overgrowth as a guiding sign of abdominal neoplasms for pediatric orthopedic surgeons.

OBJECTIVES: This study aims to increase the awareness of the association between lateralized overgrowth (LO) and abdominal tumor among the pediatric orthopedic community and to evaluate its incidence in our center. PATIENTS AND METHODS: Between January 1997 and December 2021, a total of 166 patients with Wilms tumors and hepatoblastomas were retrospectively analyzed. Data including age, sex, initial clinical signs (hematuria, abdominal mass with or without general discomfort), type of asymmetric regional body overgrowth (isolated or in relation with any syndrome), and tumor stage at diagnosis were recorded. In addition, age at which asymmetric regional body overgrowth was described and age at the time of tumor diagnosis were noted. RESULTS: Of a total of 166 patients, 133 were diagnosed with Wilms tumors (nephroblastomas) and 33 were diagnosed with hepatoblastomas. In 94% of the cases, the initial clinical signs were an abdominal mass and/or hematuria. Overall, five (3%) patients presented with LO. Four patients with Wilms tumor presented it at the initial clinical examinations. In three of these cases (2.3%), we found it isolated and, in the remaining patient (0.75%), it was associated with Beckwith-Wiedemann spectrum. Only one patient affected from hepatoblastoma (3%) presented with an isolated LO at the time of tumor diagnosis. CONCLUSION: Our study results show an incidence of LO in relation to intra-abdominal tumors of 3%. The latest updates recommend genetic testing to identify subgroups with a higher risk for tumor development that are more likely to benefit from tumor protocol surveillance.

Development of anaplastic Wilms tumor and subsequent relapse in a child with diaphanospondylodysostosis.

Diaphanospondylodysostosis (DSD) is a rare skeletal dysplasia syndrome resulting from disordered mesenchymal differentiation. Children with DSD generally die in utero or during the first month of life from severe thoracic insufficiency syndrome. An association of DSD with nephroblastomatosis has been observed, but the natural history of such nephroblastomatosis remains poorly characterized due to the rarity of the underlying condition. We describe a patient with DSD who developed bilateral hyperplastic nephroblastomatosis that ultimately evolved into therapy-resistant anaplastic Wilms tumor (nephroblastoma).