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Cancer Feb 2021WAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies, and range of developmental delays) is a rare contiguous gene deletion syndrome with a 45% to 60% risk of...
BACKGROUND
WAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies, and range of developmental delays) is a rare contiguous gene deletion syndrome with a 45% to 60% risk of developing Wilms tumor (WT). Currently, surveillance and treatment recommendations are based on limited evidence.
METHODS
Clinical characteristics, treatments, and outcomes were analyzed for patients with WAGR and WT/nephroblastomatosis who were identified through International Society of Pediatric Oncology Renal Tumor Study Group (SIOP-RTSG) registries and the SIOP-RTSG network (1989-2019). Events were defined as relapse, metachronous tumors, or death.
RESULTS
Forty-three patients were identified. The median age at WT/nephroblastomatosis diagnosis was 22 months (range, 6-44 months). The overall stage was available for 40 patients, including 15 (37.5%) with bilateral disease and none with metastatic disease. Histology was available for 42 patients; 6 nephroblastomatosis without further WT and 36 WT, including 19 stromal WT (52.8%), 12 mixed WT (33.3%), 1 regressive WT (2.8%) and 2 other/indeterminable WT (5.6%). Blastemal type WT occurred in 2 patients (5.6%) after prolonged treatment for nephroblastomatosis; anaplasia was not reported. Nephrogenic rests were present in 78.9%. Among patients with WT, the 5-year event-free survival rate was 84.3% (95% confidence interval, 72.4%-98.1%), and the overall survival rate was 91.2% (95% confidence interval, 82.1%-100%). Events (n = 6) did not include relapse, but contralateral tumor development (n = 3) occurred up to 7 years after the initial diagnosis, and 3 deaths were related to hepatotoxicity (n = 2) and obstructive ileus (n = 1).
CONCLUSIONS
Patients with WAGR have a high rate of bilateral disease and no metastatic or anaplastic tumors. Although they can be treated according to existing WT protocols, intensive monitoring of toxicity and surveillance of the remaining kidney(s) are advised.
LAY SUMMARY
WAGR syndrome (Wilms tumor, aniridia, genitourinary anomalies, and range of developmental delays) is a rare genetic condition with an increased risk of developing Wilms tumor. In this study, 43 patients with WAGR and Wilms tumor (or Wilms tumor precursor lesions/nephroblastomatosis) were identified through the international registry of the International Society of Pediatric Oncology Renal Tumor Study Group (SIOP-RTSG) and the SIOP-RTSG network. In many patients (37.5%), both kidneys were affected. Disease spread to other organs (metastases) did not occur. Overall, this study demonstrates that patients with WAGR syndrome and Wilms tumor can be treated according to existing protocols. However, intensive monitoring of treatment complications and surveillance of the remaining kidney(s) are advised.
Topics: Anaplasia; Antineoplastic Protocols; Child, Preschool; Drug-Related Side Effects and Adverse Reactions; Female; Gene Deletion; Humans; Infant; Kidney; Liver; Male; Progression-Free Survival; Risk Factors; WAGR Syndrome; Wilms Tumor
PubMed: 33146894
DOI: 10.1002/cncr.33304 -
NMC Case Report Journal Sep 2020A 6-year-old female was incidentally found to have a brain tumor. Magnetic resonance imaging (MRI) demonstrated a gadolinium-enhanced mass in the left parietal lobe. We...
A 6-year-old female was incidentally found to have a brain tumor. Magnetic resonance imaging (MRI) demonstrated a gadolinium-enhanced mass in the left parietal lobe. We performed gross total resection with the assistance of fluorescent guidance by 5-aminolevulinic acid (5-ALA). A histological examination of the tumor specimen showed well-differentiated astroblastic features with focal anaplasia. Fluorescence hybridization (FISH) revealed meningioma 1 () gene alteration and supported our diagnosis. She received local radiotherapy and oral temozolomide followed by maintenance temozolomide chemotherapy, and the tumor was well controlled without any neurological deficit for 27 months. Our case is considered to be valuable since it describes a patient who is diagnosed to have a well-differentiated astroblastoma with both focal anaplastic features and gene rearrangement. A larger study is warranted to establish evidence supporting the diagnosis and treatment of astroblastoma with molecular characteristic features. alteration will be a diagnostic marker for astroblastoma in the future.
PubMed: 33062570
DOI: 10.2176/nmccrj.cr.2020-0028 -
Case Reports in Pathology 2020Medulloblastoma is an embryonal neuroepithelial tumor that affects mainly childhood and more rarely adults. Medulloblastoma occurring as multiple nodules at diagnosis is...
Medulloblastoma is an embryonal neuroepithelial tumor that affects mainly childhood and more rarely adults. Medulloblastoma occurring as multiple nodules at diagnosis is a rare and tricky presentation. Here, we describe the case of a previously healthy 47-year-old woman with multiple posterior fossa cerebellar tumors. Histological, immunohistochemical, and molecular analyses were performed to best characterize the two excised lesions. The histopathological analysis revealed different variants of medulloblastoma in the excised nodules, one being extensive nodularity, rare in adults, and the other desmoplastic/nodular with areas of anaplasia. Immunostains and molecular analysis classified both nodules as SHH medulloblastoma. Adult medulloblastoma is extremely rare. Important differences exist between adult medulloblastoma and medulloblastoma arising in children and infants. Such differences are in location, distribution of histological variants and of molecular subgroups, survival rates, and therapeutic options. An extensive morphological and molecular characterization of such rare tumors is necessary to choice the best-tailored therapy.
PubMed: 33005468
DOI: 10.1155/2020/4502878 -
Neurologia Sep 2020No formal indication currently exists for seizure prophylaxis in neurosurgical oncology patients. Neither have specific recommendations been made on the use of... (Review)
Review
INTRODUCTION
No formal indication currently exists for seizure prophylaxis in neurosurgical oncology patients. Neither have specific recommendations been made on the use of antiepileptic drugs (AED) in seizure-free patients with meningiomas scheduled for surgery. AEDs are generally prescribed on a discretionary basis, taking into consideration a range of clinical and radiological risk factors. We present a systematic review and meta-analysis exploring the effectiveness of antiepileptic prophylaxis in patients with meningioma and no history of seizures.
METHODS
We performed a systematic review of the PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Embase, and clinicaltrials.gov databases. Of a total of 4368 studies initially identified, 12 were selected for extraction of data and qualitative analysis. Based on the clinical data presented, we were only able to include 6 studies in the meta-analysis. We performed heterogeneity studies, calculated a combined odds ratio, evaluated publication bias, and conducted a sensitivity analysis.
RESULTS
AED prophylaxis in patients with meningioma and no history of seizures did not significantly reduce the incidence of post-operative seizures in comparison to controls (Mantel-Haenszel combined odds ratio, random effects model: 1.26 [95% confidence interval, 0.60-2.78]; 2041 patients). However, we are unable to establish a robust recommendation against this treatment due to the lack of prospective studies, the presence of selection bias in the studies reviewed, the likelihood of underestimation of seizure frequency during follow-up, and the strong influence of one study on the overall effect.
CONCLUSIONS
Despite the limitations of this review, the results of the meta-analysis do not support the routine use of seizure prophylaxis in patients with meningioma and no history of seizures.
PubMed: 32896461
DOI: 10.1016/j.nrl.2020.06.014 -
The Malaysian Journal of Pathology Aug 2020Majority of Wilms tumour (WT) responds well to pre-operative chemotherapy. In Malaysia, incidence of WT is rare with only two cases reported per one million populations...
INTRODUCTION
Majority of Wilms tumour (WT) responds well to pre-operative chemotherapy. In Malaysia, incidence of WT is rare with only two cases reported per one million populations yearly. This case report is to highlight on the awareness of WT in an Asian population and highlight two cases and challenges faced after pre-operative chemotherapy.
CASE REPORT
In this case series, we report on two cases of WT which had poor response to pre-operative chemotherapy. Both cases underwent surgery after pre-operative chemotherapy and recovery was uneventful during a two-year follow-up.
DISCUSSION
Both patients had chemotherapy prior planned surgery, but had unfortunate poor tumour response. The tumour progressed in size which required a radical nephrectomy. The histology report for the first case had more than 60% blastemal cells remaining despite giving pre-operative chemotherapy with no focal anaplasia. This showed poor response to chemotherapy evidenced by the high number of blastemal cells. The second case was a stromal type WT which is known for poor response and may lead to enhancement of growth and maturation induced by chemotherapy. These were the possible reason of poor response of WT in these two cases.
Topics: Antineoplastic Combined Chemotherapy Protocols; Humans; Infant; Kidney Neoplasms; Malaysia; Male; Nephrectomy; Risk Factors; Wilms Tumor
PubMed: 32860380
DOI: No ID Found -
Frontiers in Pediatrics 2020Wilms tumor (WT) is the most frequently diagnosed malignant renal tumor in children. With current treatments, ~90% of children diagnosed with WT survive and generally...
Wilms tumor (WT) is the most frequently diagnosed malignant renal tumor in children. With current treatments, ~90% of children diagnosed with WT survive and generally present with tumors characterized by favorable histology (FHWT), whereas prognosis is poor for the remaining 10% of cases where the tumors are characterized by cellular diffuse anaplasia (DAWT). Relatively few studies have investigated microRNA-related epigenetic regulation and its relationship with altered gene expression in WT. Here, we aim to identify microRNAs differentially expressed in WT and describe their expression in terms of cellular anaplasia, metastasis, and association with the main genetic alterations in WT to identify potential prognostic biomarkers. Expression profiling using TaqMan low-density array was performed in a discovery cohort consisting of four DAWT and eight FHWT samples. Relative quantification resulted in the identification of 109 (48.7%) microRNAs differentially expressed in both WT types. Of these, miR-10a-5p, miR-29a-3p, miR-181a-5p, miR-200b-3p, and miR-218-5p were selected and tested by RT-qPCR on a validation cohort of 53 patient samples. MiR-29a and miR-218 showed significant differences in FHWT with low ( = 0.0018) and high ( = 0.0131) expression, respectively. To discriminate between miRNA expression FHWTs and healthy controls, the receiver operating characteristic (ROC) curves were obtained; miR-29a AUC was 0.7843. Furthermore, low expression levels of miR-29a and miR-200b ( = 0.0027 and = 0.0248) were observed in metastatic tumors. ROC curves for miR-29a discriminated metastatic patients (AUC = 0.8529) and miR-200b (AUC = 0.7757). To confirm the differences between cases with poor prognosis, we performed hybridization for three microRNAs in five DAWT and 17 FHWT samples, and only significant differences between adjacent tissues and FHWT tumors were found for miR-181a, miR-200b, and miR-218, in both total pixels and nuclear analyses. Analysis of copy number variation in genes showed that the most prevalent alterations were (47%), (21%), 1q (36%) gain, 1p36 (16%), and deletion/1q duplicate (26%). The five microRNAs evaluated are involved in the Hippo signaling pathway and participate in Wilms tumor development through their effects on differentiation, proliferation, angiogenesis, and metastasis.
PubMed: 32766179
DOI: 10.3389/fped.2020.00337 -
Journal of Mid-life Health 2020Endometrial stromal sarcoma (ESS) is a rare malignant tumor that constitutes about 0.2% of all uterine malignancies and 10% of uterine sarcomas. ESS is generally...
Endometrial stromal sarcoma (ESS) is a rare malignant tumor that constitutes about 0.2% of all uterine malignancies and 10% of uterine sarcomas. ESS is generally misdiagnosed as leiomyoma or endometrial polyp and typically discovered on histopathological examination postoperatively because of its rarity. Endometrial stromal tumors are composed of cells resembling normal endometrial stroma in its proliferative phase. The histologic diagnosis of the high grade is made if there is a high-grade sarcoma with a high mitotic index and nuclear anaplasia. The mean age of presentation of high-grade endometrial sarcoma is about 61 years with the most common presenting complaint is menorrhagia. The median overall survival for high-grade endometrial sarcoma is 53 months with optimal cytoreduction. A 49-year-old woman P2 L2 presented with nonspecific complaint of discharge and spotting per vaginum. In the present case, the provisional diagnosis by clinical findings as well as imaging was in favor of the inversion of submucous fibroid. Preoperative histopathological examination and immunohistochemistry confirmed the diagnosis of high-grade undifferentiated ESS. Haultain's operation followed by total abdominal hysterectomy and bilateral salpingo-oophorectomy was performed. The patient was referred to another center for radiotherapy. From there, she was lost to follow-up. Rarity of endometrial stromal tumor limits the clinician view to diagnose it preoperatively. We were fortunate to have preoperative histopathological diagnosis of ESS. Furthermore, as ESS is rare and undifferentiated stromal sarcoma is even rarer, literature is lacking on its optimal management. Hence, it is important for all clinicians to keep the high degree of suspicion for ESS while working up any case of abnormal uterine bleeding.
PubMed: 32684727
DOI: 10.4103/jmh.JMH_75_19 -
Cancer Aug 2020A primary objective of Children's Oncology Group study AREN0534 (Treatment for Patients With Multicentric or Bilaterally Predisposed, Unilateral Wilms Tumor) was to... (Clinical Trial)
Clinical Trial
BACKGROUND
A primary objective of Children's Oncology Group study AREN0534 (Treatment for Patients With Multicentric or Bilaterally Predisposed, Unilateral Wilms Tumor) was to facilitate partial nephrectomy in 25% of children with bilaterally predisposed unilateral tumors (Wilms tumor/aniridia/genitourinary anomalies/range of developmental delays [WAGR] syndrome; and multifocal and overgrowth syndromes). The purpose of this prospective study was to achieve excellent event-free survival (EFS) and overall survival (OS) while preserving renal tissue through preoperative chemotherapy, completing definitive surgery by 12 weeks from diagnosis, and modifying postoperative chemotherapy based on histologic response.
METHODS
The treating institution identified whether a predisposition syndrome existed. Patients underwent a central review of imaging studies through the biology and classification study AREN03B2 and then were eligible to enroll on AREN0534. Patients were treated with induction chemotherapy determined by localized or metastatic disease on imaging (and histology if a biopsy had been undertaken). Surgery was based on radiographic response at 6 or 12 weeks. Further chemotherapy was determined by histology. Patients who had stage III or IV disease with favorable histology received radiotherapy as well as those who had stage I through IV anaplasia.
RESULTS
In total, 34 patients were evaluable, including 13 males and 21 females with a mean age at diagnosis of 2.79 years (range, 0.49-8.78 years). The median follow-up was 4.49 years (range, 1.67-8.01 years). The underlying diagnosis included Beckwith-Wiedemann syndrome in 9 patients, hemihypertrophy in 9 patients, multicentric tumors in 10 patients, WAGR syndrome in 2 patients, a solitary kidney in 2 patients, Denys-Drash syndrome in 1 patient, and Simpson-Golabi-Behmel syndrome in 1 patient. The 4-year EFS and OS rates were 94% (95% CI, 85.2%-100%) and 100%, respectively. Two patients relapsed (1 tumor bed, 1 abdomen), and none had disease progression during induction. According to Response Evaluation Criteria in Solid Tumor 1.1 criteria, radiographic responses included a complete response in 2 patients, a partial response in 21 patients, stable disease in 11 patients, and progressive disease in 0 patients. Posttherapy histologic classification was low-risk in 13 patients (including the 2 complete responders), intermediate-risk in 15 patients, and high-risk in 6 patients (1 focal anaplasia and 5 blastemal subtype). Prenephrectomy chemotherapy facilitated renal preservation in 22 of 34 patients (65%).
CONCLUSIONS
A standardized approach of preoperative chemotherapy, surgical resection within 12 weeks, and histology-based postoperative chemotherapy results in excellent EFS, OS, and preservation of renal parenchyma.
Topics: Child; Child, Preschool; Combined Modality Therapy; Drug Therapy; Female; Humans; Infant; Kidney; Male; Neoplasm Metastasis; Nephrectomy; Progression-Free Survival; Treatment Outcome; WAGR Syndrome; Wilms Tumor
PubMed: 32459384
DOI: 10.1002/cncr.32958 -
Molecular Cancer Research : MCR Aug 2020Aqueous humor contains tumor-derived cell-free DNA (cfDNA) and can serve as a liquid biopsy for retinoblastoma. We previously associated somatic copy-number alteration...
Aqueous humor contains tumor-derived cell-free DNA (cfDNA) and can serve as a liquid biopsy for retinoblastoma. We previously associated somatic copy-number alteration (SCNA) 6p gain with a 10-fold increased risk of enucleation. Here we provide a 2-year update to further explore 6p gain as a prognostic biomarker for ocular survival. Patients diagnosed with retinoblastoma from December 2014 to July 2019 from whom aqueous humor was sampled were included. cfDNA was extracted and shallow whole-genome sequencing performed to identify highly recurrent retinoblastoma SCNAs (gain of 1q, 2p, 6p, loss of 13q, 16q). 116 aqueous humor samples from 50 eyes of 46 patients were included: 27 eyes were salvaged, 23 were enucleated. Highly recurrent retinoblastoma SCNAs were found in 66% eyes. 6p gain was the most prevalent SCNA (50% eyes). It was particularly more prevalent in enucleated eyes (73.9%) than in salvaged eyes (29.6%; = 0.004). 6p gain in aqueous humor cfDNA portended nearly 10-fold increased odds of enucleation (OR = 9.87; 95% confidence interval = 1.75-55.65; = 0.009). In the enucleated eyes, 6p gain was associated with aggressive histopathologic features, including necrosis, higher degrees of anaplasia, and focal invasion of ocular structures. With extended follow-up and nearly double the aqueous humor samples, we continue to demonstrate 6p gain as a potential prognostic biomarker for retinoblastoma. IMPLICATIONS: Aqueous humor is a high-yield source of tumor-derived DNA in retinoblastoma eyes. Detection of 6p gain in the aqueous humor allows for targeted, patient-centered therapies based on this molecular prognostic marker. Prospective, multicenter studies with aqueous humor sampled from all eyes at diagnosis are warranted to validate these findings.
Topics: Aqueous Humor; Biomarkers, Tumor; Cell-Free Nucleic Acids; Child, Preschool; Chromosomes, Human, Pair 6; DNA Copy Number Variations; Eye Enucleation; Female; Humans; Infant; Infant, Newborn; Male; Neoplasm Staging; Prognosis; Prospective Studies; Retinal Neoplasms; Retinoblastoma; Whole Genome Sequencing
PubMed: 32434859
DOI: 10.1158/1541-7786.MCR-19-1262 -
Ophthalmology Jun 2020To determine the usefulness of a comprehensive, targeted-capture next-generation sequencing (NGS) assay for the clinical management of children undergoing enucleation...
PURPOSE
To determine the usefulness of a comprehensive, targeted-capture next-generation sequencing (NGS) assay for the clinical management of children undergoing enucleation for retinoblastoma.
DESIGN
Cohort study.
PARTICIPANTS
Thirty-two children with retinoblastoma.
METHODS
We performed targeted NGS using the UCSF500 Cancer Panel (University of California, San Francisco, San Francisco, CA) on formalin-fixed, paraffin-embedded tumor tissue along with constitutional DNA isolated from peripheral blood, buccal swab, or uninvolved optic nerve. Peripheral blood samples were also sent to a commercial laboratory for germline RB1 mutation testing.
MAIN OUTCOME MEASURES
Presence or absence of germline RB1 mutation or deletion, tumor genetic profile, and association of genetic alterations with clinicopathologic features.
RESULTS
Germline mutation or deletion of the RB1 gene was identified in all children with bilateral retinoblastoma (n = 12), and these NGS results were 100% concordant with commercial germline RB1 mutation analysis. In tumor tissue tested with NGS, biallelic inactivation of RB1 was identified in 28 tumors and focal MYCN amplification was identified in 4 tumors (2 with wild-type RB1 and 2 with biallelic RB1 inactivation). Additional likely pathogenic alterations beyond RB1 were identified in 13 tumors (41%), several of which have not been reported previously in retinoblastoma. These included focal amplifications of MDM4 and RAF1, as well as damaging mutations involving BCOR, ARID1A, MGA, FAT1, and ATRX. The presence of additional likely pathogenetic mutations beyond RB1 inactivation was associated with aggressive histopathologic features, including higher histologic grade and anaplasia, and also with both unilateral and sporadic disease.
CONCLUSIONS
Comprehensive NGS analysis reliably detects relevant mutations, amplifications, and chromosomal copy number changes in retinoblastoma. The presence of genetic alterations beyond RB1 inactivation correlates with aggressive histopathologic features.
Topics: Child; Child, Preschool; Cohort Studies; DNA Mutational Analysis; DNA, Neoplasm; Eye Enucleation; Female; Gene Silencing; Germ-Line Mutation; High-Throughput Nucleotide Sequencing; Humans; Infant; Male; Paraffin Embedding; Retinal Neoplasms; Retinoblastoma; Retinoblastoma Binding Proteins; Tissue Fixation; Ubiquitin-Protein Ligases
PubMed: 32139107
DOI: 10.1016/j.ophtha.2019.12.005