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Genetics in Medicine : Official Journal... Feb 2017Germ-line mutations in DICER1 increase the risk of various tumors, including pleuropulmonary blastoma. Macrocephaly and symmetric overgrowth have been reported in some,...
PURPOSE
Germ-line mutations in DICER1 increase the risk of various tumors, including pleuropulmonary blastoma. Macrocephaly and symmetric overgrowth have been reported in some, but not all, patients with mosaic DICER1 RNase IIIb mutations. The prevalence of these features in individuals with constitutional germ-line DICER1 mutations is unknown.
METHODS
We analyzed prospectively collected auxology data from 67 DICER1 mutation carriers and 43 family controls. We assessed differences between groups using an exact test for proportions and generalized estimating equations for continuous dependent variables.
RESULTS
Twenty-eight DICER1 mutation carriers (42%) were macrocephalic, and none had an occipitofrontal circumference (OFC) below the third centile, which significantly differed from family controls, of whom five were macrocephalic (12%) and two had OFC below the third centile (5%) (P < 0.001). DICER1 mutation carriers were taller than familial controls after controlling for gender (P = 0.048), but similar proportions of both groups were above the 97th centile of population norms. Head circumference remained increased after adjusting for differences in height.
CONCLUSION
For the first time, we establish macrocephaly as a common finding in the DICER1 syndrome. Like some other tumor-predisposition disorders, macrocephaly may be a useful, albeit a subtle, clinical clue to the DICER1 syndrome diagnosis.Genet Med 19 2, 244-248.
Topics: Adolescent; Adult; Aged; Body Height; Child; Child, Preschool; DEAD-box RNA Helicases; Female; Germ-Line Mutation; Heterozygote; Humans; Infant; Male; Megalencephaly; Middle Aged; Neoplasms; Pulmonary Blastoma; Ribonuclease III
PubMed: 27441995
DOI: 10.1038/gim.2016.83 -
International Journal of Cancer Nov 2017The DICER1 syndrome is associated with a variety of rare benign and malignant tumors, including pleuropulmonary blastoma (PPB), cystic nephroma (CN) and Sertoli-Leydig...
The DICER1 syndrome is associated with a variety of rare benign and malignant tumors, including pleuropulmonary blastoma (PPB), cystic nephroma (CN) and Sertoli-Leydig cell tumor (SLCT). The prevalence and penetrance of pathogenic DICER1 variation in the general population is unknown. We examined three publicly-available germline whole exome sequence datasets: Exome Aggregation Consortium (ExAC), 1,000 Genomes (1,000 G) and the Exome Sequencing Project (ESP). To avoid over-estimation of pathogenic DICER1 variation from cancer-associated exomes, we excluded The Cancer Genome Atlas (TCGA) variants from ExAC. All datasets were annotated with snpEff and ANNOVAR and variants were classified into four categories: likely benign (LB), unknown significance (VUS), likely pathogenic (LP), or pathogenic (P). The prevalence of DICER1 P/LP variants was 1:870 to 1:2,529 in ExAC-nonTCGA (53,105 exomes) estimated by metaSVM and REVEL/CADD, respectively. A more stringent prevalence calculation considering only loss-of-function and previously-published pathogenic variants detected in ExAC-nonTCGA, yielded a prevalence of 1:10,600. Despite the rarity of most DICER1 syndrome tumors, pathogenic DICER1 variation is more common than expected. If confirmed, these findings may inform future sequencing-based newborn screening programs for PPB, CN and SLCT, in which early detection improves prognosis.
Topics: Biomarkers; DEAD-box RNA Helicases; Early Detection of Cancer; Female; Genetic Predisposition to Disease; Germ-Line Mutation; Humans; Kidney Diseases, Cystic; Ovarian Neoplasms; Prevalence; Prognosis; Pulmonary Blastoma; Ribonuclease III; Sertoli-Leydig Cell Tumor; United States
PubMed: 28748527
DOI: 10.1002/ijc.30907 -
World Journal of Surgical Oncology Aug 2018Pleuroblastoma (PPB) is a rare pediatric tumor which, in 30% of cases, is associated with cystic nephroma. It has been recently linked to the DICER1 mutation as part of... (Review)
Review
BACKGROUND
Pleuroblastoma (PPB) is a rare pediatric tumor which, in 30% of cases, is associated with cystic nephroma. It has been recently linked to the DICER1 mutation as part of a predisposition syndrome for various tumors. However, if DICER 1 anomalies have been reported in patients with Wilms tumor (WT), to date, no cases of PPB, WT, and DICER1 mutations have been reported in the same patient.
CASE PRESENTATION
We report the case of a 3-year-old patient, initially managed for metastatic WT. During his clinical course, the diagnosis of a PPB was made after detecting the DICER1 mutation and subsequent management was therefore modified.
CONCLUSION
This case highlights that in case of simultaneous discovery of a renal tumor and a pulmonary lesion in a child, the DICER 1 mutations should be looked for as these could help adapt management and schedule the surgical procedures.
Topics: Child, Preschool; DEAD-box RNA Helicases; Female; Genetic Predisposition to Disease; Humans; Kidney Neoplasms; Lung Neoplasms; Prognosis; Pulmonary Blastoma; Ribonuclease III; Wilms Tumor
PubMed: 30097050
DOI: 10.1186/s12957-018-1469-4 -
Archivos Argentinos de Pediatria Jun 2018Pleuropulmonary Blastoma corresponds to a malignant primary lung disorder, exclusive of pediatric age, infrequent and of aggressive characteristics. Age on diagnosis is...
Pleuropulmonary Blastoma corresponds to a malignant primary lung disorder, exclusive of pediatric age, infrequent and of aggressive characteristics. Age on diagnosis is 1 month-12 years. Rates per sex are equal. It can be found inside pleura or lungs. Respiratory distress associated or not with pneumothorax, chest pain and fever are classical clinical signs. These symptoms could be misdiagnosed as pneumonia. Radiologically, a large mass near the pleura at the base of the right lung without air bronchogram is its most common form. It has three histological types: type I (cystic), type II (mixed) and type III (solid). Its treatment requires tumor excision and multimodal chemotherapy. Pleuropulmonary Blastoma type I has good prognosis; type II and III variants have lower survival. We report a 2-year-old girl, pointing to the clinicalradiological diagnosis.
Topics: Child, Preschool; Cough; Female; Hemoptysis; Humans; Prognosis; Pulmonary Blastoma; Survival
PubMed: 29756723
DOI: 10.5546/aap.2018.e455 -
OncoTargets and Therapy 2016The aim of this study was to analyze and summarize the clinicopathological and molecular characteristics of classic biphasic pulmonary blastoma (PB) to improve its...
PURPOSE
The aim of this study was to analyze and summarize the clinicopathological and molecular characteristics of classic biphasic pulmonary blastoma (PB) to improve its diagnosis and treatment.
PATIENTS AND METHODS
A retrospective analysis was performed in patients who were diagnosed with PB at Sun Yat-Sen University Cancer Center from March 1995 to March 2015. Genomic DNA was profiled using a capture-based targeted sequencing panel.
RESULTS
Sixteen patients with an average age of 40 years were included in this study. Accurate preoperative diagnosis was very challenging as surgically resected tissues with immunohistochemical staining were required for the diagnosis. Surgery was the optimal treatment for localized disease and there was no standard management for metastatic disease. Mutations were detected among 9 out of the 56 genes profiled, including , , , , , , , , and .
CONCLUSION
Due to the low incidence rate and the reclassification of PB, no standard treatment is available. Although the numbers of cases are few with varying individual experiences, it is important to improve our understanding regarding this rare lung cancer. Targeted DNA sequencing may be of clinical use for molecular testing and the effects of targeted therapy need to be confirmed.
PubMed: 27877056
DOI: 10.2147/OTT.S117097 -
International Journal of Clinical and... 2015Pulmonary blastoma is a rare series of malignant lung tumor, which contains three categories: classic biphasic pulmonary blastoma, pluropulmonary blastoma, and... (Review)
Review
Pulmonary blastoma is a rare series of malignant lung tumor, which contains three categories: classic biphasic pulmonary blastoma, pluropulmonary blastoma, and well-differentiated fetal adenocarcinoma. In this study, a 19-year old female suffering with classic biphasic pulmonary blastoma and metastases in brain and axilla was presented with special interest in clinicopathological presentations, immunohistochemical features, and molecular characterizations. However, this case was misdiagnosed initially with small biopsy specimen. Comprehensive management should be used for the treatment of this malignancy.
Topics: Axilla; Biomarkers, Tumor; Brain Neoplasms; Female; Humans; Immunohistochemistry; Lung Neoplasms; Lymphatic Metastasis; Pulmonary Blastoma; Young Adult
PubMed: 25755806
DOI: No ID Found -
Medical Archives (Sarajevo, Bosnia and... Feb 2021Pleuropulmonary blastoma (PPB) is a rare, but aggressive tumor in the pediatric population. PPB is a dysontogenetic neoplasm of childhood that involves the lungs and/or...
INTRODUCTION
Pleuropulmonary blastoma (PPB) is a rare, but aggressive tumor in the pediatric population. PPB is a dysontogenetic neoplasm of childhood that involves the lungs and/or pleura. Young relatives of children with PPB have an increased incidence of neoplasias and dysplasias. According to tumor tissue histopathology, PPB evolves from a cystic to solid state over time. PPBs can be sub-classified as type I (purely cystic), type II (having both cystic and solid elements), and type III (completely solid). Type II and type III tumors may be associated with metastasis, with the brain being the most common metastatic site. Due to the primitive nature of cells in the tumor mass, PPBs are very aggressive tumors that are resistant to therapy. The prognosis depends on the histopathology content and tumor type. Respiratory problems are the main complaint and diagnosis can be made only after additional examinations. Genetic relations through family members are associated with mutations in the DICER1 gene; between 60-80% of patients with PPBs are positive for DICER1 mutations. Mosaicism has also been reported.
AIM
The aim was to present a case of a 4 month-old infant with type II PPB, who had a negative result for DICER1 mutation in next generation sequencing. To detail the clinical presentation of this patient, we present radiographic and ultrasound findings and results of histopathological analysis, as well as genetic and scintigraphic findings and chemotherapy treatment.
CASE REPORT
Here we describe the genetic analysis of a patient with PPB who was negative for mutations in DICER1 and who had no relatives with disease. This patient underwent radical resection of the tumor and began therapy, but subsequently died after developing leukopenia and sepsis.
CONCLUSION
This case provides an example of a patient with PPB who was negative for DICER1 mutation upon genetic analysis and emphasizes the potential for disease that does not involve mutation of this gene.
Topics: Fatal Outcome; High-Throughput Nucleotide Sequencing; Humans; Infant; Lung Neoplasms; Mutation; Prognosis; Pulmonary Blastoma; Ribonuclease III
PubMed: 34012202
DOI: 10.5455/medarh.2021.75.61-65 -
Journal of Clinical Oncology : Official... Feb 2023Pleuropulmonary blastoma (PPB) is the most common primary lung neoplasm of infancy and early childhood. Type II and type III PPB have historically been associated with a...
PURPOSE
Pleuropulmonary blastoma (PPB) is the most common primary lung neoplasm of infancy and early childhood. Type II and type III PPB have historically been associated with a poor prognosis.
METHODS
Patients with known or suspected PPB were enrolled in the International PPB/ Registry. Medical records were abstracted with follow-up ascertained annually. All PPB diagnoses were confirmed by central pathology review. Beginning in 2007, the IVADo regimen (ifosfamide, vincristine, actinomycin-D, and doxorubicin) was recommended as a potential treatment regimen for children with type II and type III PPB. This regimen was compared with a historical control cohort.
RESULTS
From 1987 to 2021, 314 children with centrally confirmed type II and type III PPB who received upfront chemotherapy were enrolled; 132 children (75 with type II and 57 with type III) received IVADo chemotherapy. Adjusted analyses suggest improved overall survival for children treated with IVADo in comparison with historical controls with an estimated hazard ratio of 0.65 (95% CI, 0.39 to 1.08). Compared with localized disease, distant metastasis at diagnosis was associated with worse PPB event-free survival and overall survival with hazard ratio of 4.23 (95% CI, 2.42 to 7.38) and 4.69 (95% CI, 2.50 to 8.80), respectively.
CONCLUSION
The use of IVADo in children with type II and type III PPB resulted in similar-to-improved outcomes compared with historical controls. Inferior outcomes with metastatic disease suggest the need for novel therapies. This large cohort of uniformly treated children with advanced PPB serves as a benchmark for future multicenter therapeutic studies for this rare pediatric tumor.
Topics: Child; Humans; DEAD-box RNA Helicases; Doxorubicin; Lung Neoplasms; Pulmonary Blastoma; Registries; Ribonuclease III
PubMed: 36137255
DOI: 10.1200/JCO.21.02925 -
Frontiers in Oncology 2023Pulmonary blastoma (PB) is a rare and invasive malignancy of the lungs with a poor prognosis. Although the mainstay treatment of PB is surgery, and radiotherapy and...
Pulmonary blastoma (PB) is a rare and invasive malignancy of the lungs with a poor prognosis. Although the mainstay treatment of PB is surgery, and radiotherapy and chemotherapy have been reported, no standard therapy exists for patients inoperable in advanced stages. Moreover, little is known about driver mutation status and immunotherapy efficacy. This paper presents a male patient diagnosed with classic biphasic PB using CT-guided lung biopsy pathology and immunohistochemistry. The patient's symptoms included cough, chest pain, shortness of breath, hemoptysis, and hypodynamia. The primary focus of this paper is to discuss the impact of anti-PD-1 immunotherapy on PB. The patient experienced progression-free survival (PFS) of over 27 months following sintilimab second-line anti-PD-1 therapy. The patient has currently survived for nearly 40 months with a satisfactory quality of life.
PubMed: 37124510
DOI: 10.3389/fonc.2023.1146204 -
Monaldi Archives For Chest Disease =... Jul 2020Biphasic pulmonary blastoma (BPB) is an extremely rare highly aggressive malignant tumor that arises from fetal lung tissue and has the classical biphasic histology of... (Review)
Review
Biphasic pulmonary blastoma (BPB) is an extremely rare highly aggressive malignant tumor that arises from fetal lung tissue and has the classical biphasic histology of epithelial and mesenchymal components. It is usually seen in adults with a slight male predominance and smokers. Previously grouped along with well-differentiated fetal adenocarcinoma (WDFA), and pleuropulmonary blastoma (PPB), now it is considered a separate variant and grouped under sarcomatoid neoplasms. Symptoms include chest pain, cough, hemoptysis and it is asymptomatic in at least one-third of the cases. A biopsy is essential for diagnosis and surgical excision is the treatment of choice. Prognosis is poor with 5-year survival less than 20% and recurrence occurring within 12 months of surgery. An aggressive multimodality approach is required for its management and active follow up surveillance is needed to look for recurrence.
Topics: Adult; Aftercare; Biopsy; Bronchoscopy; Chest Pain; Cough; Fluorodeoxyglucose F18; Hemoptysis; Humans; Lung Neoplasms; Male; Neoadjuvant Therapy; Neoplasm Staging; Positron Emission Tomography Computed Tomography; Pulmonary Blastoma
PubMed: 32729706
DOI: 10.4081/monaldi.2020.1462