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Genes Aug 2023The identification of cancer predisposition syndromes (CPSs) plays a crucial role in understanding the etiology of pediatric cancers. CPSs are genetic mutations that...
The identification of cancer predisposition syndromes (CPSs) plays a crucial role in understanding the etiology of pediatric cancers. CPSs are genetic mutations that increase the risk of developing cancer at an earlier age compared to the risk for the general population. This article aims to provide a comprehensive analysis of three unique cases involving pediatric patients with CPS who were diagnosed with multiple simultaneous or metachronous cancers. The first case involves a child with embryonal rhabdomyosarcoma, nephroblastoma, glioma, and subsequent medulloblastoma. Genetic analysis identified two pathogenic variants in the gene. The second case involves a child with alveolar rhabdomyosarcoma, juvenile xanthogranuloma, gliomas, and subsequent JMML/MDS/MPS. A pathogenic variant in the gene was identified. The third case involves a child with pleuropulmonary blastoma and pediatric cystic nephroma/nephroblastoma, in whom a pathogenic variant in the gene was identified. Multiple simultaneous and metachronous cancers in pediatric patients with CPSs are a rare but significant phenomenon. Comprehensive analysis and genetic testing play significant roles in understanding the underlying mechanisms and guiding treatment strategies for these unique cases. Early detection and targeted interventions are important for improving outcomes in these individuals.
PubMed: 37761810
DOI: 10.3390/genes14091670 -
Hong Kong Medical Journal = Xianggang... Aug 2022
Topics: Child; Hong Kong; Humans; Lung Neoplasms; Pulmonary Blastoma
PubMed: 35989435
DOI: 10.12809/hkmj219503 -
JAMA Network Open Jun 2022
Topics: Humans; Lung; Pulmonary Blastoma; Radionuclide Imaging; Tomography, X-Ray Computed
PubMed: 35771580
DOI: 10.1001/jamanetworkopen.2022.19826 -
Gynecologic Oncology Dec 2017Ovarian sex cord-stromal tumors (OSCST) include juvenile granulosa cell tumors (JGCT), Sertoli-Leydig cell tumor (SLCT) and gynandroblastoma (GAB) among others. These...
BACKGROUND
Ovarian sex cord-stromal tumors (OSCST) include juvenile granulosa cell tumors (JGCT), Sertoli-Leydig cell tumor (SLCT) and gynandroblastoma (GAB) among others. These ovarian sex cord-stromal tumors as well as other tumors including pleuropulmonary blastoma (PPB) may be associated with DICER1 mutations. We sought to describe the clinical and genetic findings from the first 107 individuals enrolled in the International Ovarian and Testicular Stromal Tumor Registry.
METHODS
Medical and family history were obtained for individuals consecutively enrolled in the International Ovarian and Testicular Stromal Tumor Registry. Pathology was centrally reviewed. DICER1 sequencing was performed on blood and tumor tissue.
RESULTS
Of the 107 participants, 49 had SLCT, 25 had JGCT and 5 had GAB. Nearly all (36/37) SLCTs and 4/4 GAB tested had a DICER1 mutation in an RNase IIIb domain hotspot; approximately half of these individuals had a predisposing germline DICER1 mutation. Metachronous SLCTs were seen in 3 individuals with germline DICER1 mutations. Other DICER1-associated conditions were seen in 19% of patients with SLCT or GAB. Three children of women with SLCT were diagnosed with PPB based on genetic testing and clinical screening during the course of this study. All were diagnosed with PPB in its earliest and most curable form (Type I), were treated with surgery alone, and are alive without evidence of disease.
CONCLUSIONS
Recognition of the distinct genetic basis for a group of these tumors improves precise classification in difficult cases and promotes mutation-based screening and early detection.
Topics: Adolescent; Adult; Child; Child, Preschool; DEAD-box RNA Helicases; Female; Genetic Predisposition to Disease; Germ-Line Mutation; Humans; Infant; Middle Aged; Mosaicism; Ovarian Neoplasms; Prognosis; Registries; Ribonuclease III; Sertoli-Leydig Cell Tumor; Sex Cord-Gonadal Stromal Tumors; Young Adult
PubMed: 29037807
DOI: 10.1016/j.ygyno.2017.09.034 -
Molecular Genetics & Genomic Medicine Mar 2019The DICER1 syndrome is an autosomal dominant tumor-predisposition disorder associated with pleuropulmonary blastoma, a rare pediatric lung cancer. Somatic missense...
BACKGROUND
The DICER1 syndrome is an autosomal dominant tumor-predisposition disorder associated with pleuropulmonary blastoma, a rare pediatric lung cancer. Somatic missense variation in "hotspot" codons in the RNaseIIIb domain (E1705, D1709, G1809, D1810, E1813) is observed in DICER1-associated tumors. Previously, we found the prevalence of germline pathogenic DICER1 variation in the general population is 1:10,600. In this study, we investigated the prevalence of pathogenic DICER1 germline variation in The Cancer Genome Atlas (TCGA; 32 adult cancer types; 9,173 exomes) and the Therapeutically Applicable Research to Generate Effective Treatment (TARGET; two pediatric cancer types; 175 exomes) cohorts.
METHODS
All datasets were annotated and binned into four categories: pathogenic, likely pathogenic, variant of unknown significance, or likely benign.
RESULTS
The prevalence of DICER1 pathogenic variants was 1:4,600 in TCGA. A single participant with a uterine corpus endometrial carcinoma harbored two pathogenic germline DICER1 (hotspot and splice-donor) variants, and a single participant with a rectal adenocarcinoma harbored a germline DICER1 stop-gained variant. In the smaller TARGET dataset, we observed no pathogenic germline variants.
CONCLUSION
This is the largest comprehensive analysis of DICER1 pathogenic variation in adult and pediatric cancer populations using publicly available data. The observation of germline DICER1 variation with uterine corpus endometrial carcinoma merits additional investigation.
Topics: DEAD-box RNA Helicases; Datasets as Topic; Germ-Line Mutation; Humans; Neoplasms; Polymorphism, Genetic; Ribonuclease III
PubMed: 30672147
DOI: 10.1002/mgg3.555 -
Cureus Dec 2021Pleuropulmonary blastoma (PPB) is a rare pediatric cancer, and although there have been improvements in its treatment approach, recurrences retain a very poor prognosis....
Pleuropulmonary blastoma (PPB) is a rare pediatric cancer, and although there have been improvements in its treatment approach, recurrences retain a very poor prognosis. Here, we report a case of a 30-month-old female who survived recurrent PPB after undergoing surgery, adjuvant chemotherapy, intrapleural cisplatin infusion, and targeted therapy through whole exome sequencing (WES). Intrapleural cisplatin infusion and target therapy appear to be safe and can be considered in a multimodal approach for the management of recurrent PPB.
PubMed: 35103161
DOI: 10.7759/cureus.20584 -
The Pan African Medical Journal 2022Pleuropulmonary blastoma is a rare intrathoracic tumor in children. It is associated with poor prognosis and diagnosis is based on histological examination. We conducted...
Pleuropulmonary blastoma is a rare intrathoracic tumor in children. It is associated with poor prognosis and diagnosis is based on histological examination. We conducted a didactic study involving a 3-year-old child with severe acute respiratory distress associated with hemothorax; radiological and thoracoscopic examination suggested malignant pleuropulmonary process. Anatomopathological examination with radio-clinical comparison allowed for the diagnosis of solid-cystic pleuropulmonary blastoma type II. Unfortunately, given the severity of the clinical features, the child died within a few weeks due to multiple organ failure. Pathologist experience is very important to recognize the disease and to start adequate treatment as soon as possible. This allows for a tumor regression rate up to 90% after neoadjuvant treatment and a 5-year survival rate of at least 53% for aggressive forms: solid and solido-cystic tumors.
Topics: Humans; Child, Preschool; Lung Neoplasms; Pulmonary Blastoma; Neoadjuvant Therapy; Radiography
PubMed: 36284883
DOI: 10.11604/pamj.2022.43.8.33823 -
Ophthalmology Feb 2019To characterize the ocular phenotype of DICER1 syndrome.
PURPOSE
To characterize the ocular phenotype of DICER1 syndrome.
DESIGN
Prospective, single-center, case-control study.
PARTICIPANTS
One hundred three patients with an identified germline pathogenic DICER1 variant (DICER1 carriers) and 69 family control participants underwent clinical and ophthalmic examination at the National Institutes of Health between 2011 and 2016.
METHODS
All participants were evaluated with a comprehensive ophthalmic examination, including best-corrected visual acuity, slit-lamp biomicroscopy, and a dilated fundus examination. A subset of patients returned for a more detailed evaluation including spectral-domain OCT, color fundus photography, fundus autofluorescence imaging, visual field testing, full-field electroretinography, and genetic testing for inherited retinal degenerative diseases.
MAIN OUTCOME MEASURES
Visual acuity and examination findings.
RESULTS
Most DICER1 carriers (97%) maintained a visual acuity of 20/40 or better in both eyes. Twenty-three DICER1 carriers (22%) showed ocular abnormalities compared with 4 family controls (6%; P = 0.005). These abnormalities included retinal pigment abnormalities (n = 6 [5.8%]), increased cup-to-disc ratio (n = 5 [4.9%]), optic nerve abnormalities (n = 2 [1.9%]), epiretinal membrane (n = 2 [1.9%]), and drusen (n = 2 [1.9%]). Overall, we observed a significant difference (P = 0.03) in the rate of retinal abnormalities in DICER1 carriers (n = 11 [11%]) versus controls (n = 1 [1.5%]). One patient demonstrated an unexpected diagnosis of retinitis pigmentosa with a novel variant of unknown significance in PRPF31, and 1 showed optic nerve elevation in the setting of increased intracranial pressure (ICP) of unclear cause. Three patients (3%) demonstrated DICER1-related ciliary body medulloepithelioma (CBME), 2 of which were identified during routine examination, a higher rate than that reported previously.
CONCLUSIONS
Ophthalmologists should be aware of the ophthalmic manifestations of DICER1 syndrome, and individuals and families should be counseled on the potential signs and symptoms. We recommend that children with a germline pathogenic variant in DICER1, especially those younger than 10 years, undergo annual dilated ophthalmic examination, looking for evidence of CBME, signs of increased ICP, and perhaps changes in the retinal pigment epithelium.
Topics: Adolescent; Adult; Aged; Case-Control Studies; Child; Child, Preschool; Ciliary Body; DEAD-box RNA Helicases; DNA, Neoplasm; Electroretinography; Female; Gene Expression Regulation, Neoplastic; Genetic Predisposition to Disease; Humans; Infant; Male; Middle Aged; Neuroectodermal Tumors, Primitive; Phenotype; Prospective Studies; Retinal Pigment Epithelium; Ribonuclease III; Slit Lamp Microscopy; Syndrome; Tomography, Optical Coherence; Uveal Neoplasms; Visual Acuity; Young Adult
PubMed: 30339877
DOI: 10.1016/j.ophtha.2018.09.038 -
JAMA Network Open Jun 2022The ability of computed tomography (CT) to distinguish between benign congenital lung malformations and malignant cystic pleuropulmonary blastomas (PPBs) is unclear.
IMPORTANCE
The ability of computed tomography (CT) to distinguish between benign congenital lung malformations and malignant cystic pleuropulmonary blastomas (PPBs) is unclear.
OBJECTIVE
To assess whether chest CT can detect malignant tumors among postnatally detected lung lesions in children.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective multicenter case-control study used a consortium database of 521 pathologically confirmed primary lung lesions from January 1, 2009, through December 31, 2015, to assess diagnostic accuracy. Preoperative CT scans of children with cystic PPB (cases) were selected and age-matched with CT scans from patients with postnatally detected congenital lung malformations (controls). Statistical analysis was performed from January 18 to September 6, 2020. Preoperative CT scans were interpreted independently by 9 experienced pediatric radiologists in a blinded fashion and analyzed from January 24, 2019, to September 6, 2020.
MAIN OUTCOMES AND MEASURES
Accuracy, sensitivity, and specificity of CT in correctly identifying children with malignant tumors.
RESULTS
Among 477 CT scans identified (282 boys [59%]; median age at CT, 3.6 months [IQR, 1.2-7.2 months]; median age at resection, 6.9 months [IQR, 4.2-12.8 months]), 40 cases were extensively reviewed; 9 cases (23%) had pathologically confirmed cystic PPB. The median age at CT was 7.3 months (IQR, 2.9-22.4 months), and median age at resection was 8.7 months (IQR, 5.0-24.4 months). The sensitivity of CT for detecting PPB was 58%, and the specificity was 83%. High suspicion for malignancy correlated with PPB pathology (odds ratio, 13.5; 95% CI, 2.7-67.3; P = .002). There was poor interrater reliability (κ = 0.36 [range, 0.06-0.64]; P < .001) and no significant difference in specific imaging characteristics between PPB and benign cystic lesions. The overall accuracy rate for distinguishing benign vs malignant lesions was 81%.
CONCLUSIONS AND RELEVANCE
This study suggests that chest CT, the current criterion standard imaging modality to assess the lung parenchyma, may not accurately and reliably distinguish PPB from benign congenital lung malformations in children. In any cystic lung lesion without a prenatal diagnosis, operative management to confirm pathologic diagnosis is warranted.
Topics: Case-Control Studies; Child; Female; Humans; Lung; Lung Diseases; Lung Neoplasms; Male; Pregnancy; Pulmonary Blastoma; Reproducibility of Results; Tomography, X-Ray Computed
PubMed: 35771571
DOI: 10.1001/jamanetworkopen.2022.19814 -
Pediatric Blood & Cancer Jun 2023Pediatric pulmonary malignancy can be primary or metastatic, with the latter being by far the more common. With a few exceptions, there are no well-established...
Pediatric pulmonary malignancy can be primary or metastatic, with the latter being by far the more common. With a few exceptions, there are no well-established evidence-based guidelines for imaging pediatric pulmonary malignancies, although computed tomography (CT) is used in almost all cases. The aim of this article is to provide general imaging guidelines for pediatric pulmonary malignancies, including minimum standards for cross-sectional imaging techniques and specific imaging recommendations for select entities.
Topics: Child; Humans; Pulmonary Blastoma; Surface Plasmon Resonance; Lung Neoplasms; Lung; Tomography, X-Ray Computed
PubMed: 36121877
DOI: 10.1002/pbc.29964