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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 -
Archivos Argentinos de Pediatria Feb 2016Pleuropulmonary blastoma is a rare lung tumor of childhood that can occur with cystic or solid lesions, as a radiological finding with or without respiratory symptoms....
Pleuropulmonary blastoma is a rare lung tumor of childhood that can occur with cystic or solid lesions, as a radiological finding with or without respiratory symptoms. We report the case of a 2 year old toddler in his first pulmonary obstructive episode with suspected toracic malformation of the left upper lobe in his chest x-ray and tomography. Surgery was performed showing cystic malformation of the left upper lobe. We received the pathology report with diagnosis of type I pleuropulmonary blastoma. He began follow-up with Oncology initiating treatment with cyclophosphamide and vincristine, well tolerated. Currently, there is controversy about the management of congenital lung cysts, tilting the balance towards the surgical procedure because of serious difficulties in differentiating benign pulmonary cysts from pleuropulmonary blastoma without histopathologic review.
Topics: Child, Preschool; Humans; Lung Neoplasms; Male; Pulmonary Blastoma; Tomography, X-Ray Computed
PubMed: 26914086
DOI: 10.5546/aap.2016.e25 -
Turk Patoloji Dergisi 2015Pleuropulmonary blastoma is rare embryonal tumor of infancy and early childhood and it often arises from lung and more rarely from the parietal pleura. We present this...
Pleuropulmonary blastoma is rare embryonal tumor of infancy and early childhood and it often arises from lung and more rarely from the parietal pleura. We present this entity which has no systematic data associated with its incidence in order to discuss clinical, histopathological, immunohistochemical features and the differential diagnosis. A three-year-old boy presented with fever showed signs of upper respiratory tract infection. Radiological examination revealed a solid mass filling the right hemithorax. The patient underwent core needle biopsy, wedge biopsy and lobectomy. Biopsy and surgical material were examined histopathologically. The tumor was composed of predominantly solid areas consisting blastemal cells with spindle, polygonal and round nuclei in the myxoid stroma. Immunohistochemical staining of the tumor cells were positive with vimentin and desmin. MIB-1 labeling index was above 90%. Histological diagnosis was pleuropulmonary blastoma type 3. The surgically sampled adjacent diafragma was also infiltrated with the tumor. The patient was treated with chemotherapy and showed no signs of recurrence in the follow-up of 9 months. Pleuropulmonary blastoma is a very rare childhood cancer that needs to be kept in mind in the pathological differential diagnosis of thoracic tumors in the children.
Topics: Biomarkers, Tumor; Biopsy, Needle; Chemotherapy, Adjuvant; Child, Preschool; Diagnosis, Differential; Humans; Immunohistochemistry; Magnetic Resonance Imaging; Male; Pneumonectomy; Predictive Value of Tests; Pulmonary Blastoma; Time Factors; Treatment Outcome
PubMed: 25560611
DOI: No ID Found -
Turk Gogus Kalp Damar Cerrahisi Dergisi Jan 2020Pleuropulmonary blastoma is a rare and aggressive childhood tumor of mesenchymal origin. It has a poor prognosis and mainly classified as cystic (type 1), mixed type...
Pleuropulmonary blastoma is a rare and aggressive childhood tumor of mesenchymal origin. It has a poor prognosis and mainly classified as cystic (type 1), mixed type (type 2), and solid (type 3). Herein, we present two cases of pleuropulmonary blastoma type 3 presenting with pneumothorax, a rare clinical presentation of pleuropulmonary blastoma, which was successfully treated with surgery.
PubMed: 32175165
DOI: 10.5606/tgkdc.dergisi.2020.18215 -
Problemy Endokrinologii Oct 2023DICER1 syndrome is a rare genetic disorder with the progressive development of malignant and non-malignant diseases in childhood. The cause of this syndrome is a... (Review)
Review
DICER1 syndrome is a rare genetic disorder with the progressive development of malignant and non-malignant diseases in childhood. The cause of this syndrome is a dusfunction of the endoribonuclease DICER, which plays an important role in the processing of microRNAs with subsequent regulation of the control of the expression of oncogenes and tumor suppressor genes. Clinical manifestations of dyseropathies is very different and may include both endocrine manifestations - multinodular goiter, differentiated thyroid cancers, ovarian stromal tumors, pituitary blastoma, and non-endocrine formations - pleuropulmonary blastoma, cystic nephroma, pineoblastoma. The presence of somatic mutations of the DICER1 gene is a resultant stage in the pathogenesis of dyseropathies, determining the further path of oncogenesis. At present, DICER1 syndrome is diagnosed extremely rarely, which leads to late detection of the components of the disease in the patient, late diagnosis of neoplasms, lack of family counseling. Diagnosis at the early stages of the disease, the development of screening programs for the management of these patients allows minimizing the risks of developing more malignant, aggressive forms of the disease.
Topics: Humans; Ribonuclease III; DEAD-box RNA Helicases; Mutation; Female; Thyroid Neoplasms; Goiter, Nodular; Pulmonary Blastoma
PubMed: 38796764
DOI: 10.14341/probl13383 -
JCO Precision Oncology Sep 2023Germline pathogenic loss-of-function (pLOF) variants in are associated with a predisposition for a variety of solid neoplasms, including pleuropulmonary blastoma and...
Germline pathogenic loss-of-function (pLOF) variants in are associated with a predisposition for a variety of solid neoplasms, including pleuropulmonary blastoma and Sertoli-Leydig cell tumor (SLCT). The most common pLOF variants include small insertions or deletions leading to frameshifts, and base substitutions leading to nonsense codons or altered splice sites. Larger deletions and pathogenic missense variants occur less frequently. Identifying these variants can trigger surveillance algorithms with potential for early detection of -related cancers and cascade testing of family members. However, some patients with -associated tumors have no pLOF variants detected by germline or tumor testing. Here, we present two patients with SLCT whose tumor sequencing showed only a somatic missense RNase IIIb variant. Conventional exon-directed germline sequencing revealed no pLOF variants. Using a custom capture panel, we discovered novel intronic variants, ENST00000343455.7: c.1752+213A>G and c.1509+16A>G, that appear to interfere with normal splicing. We suggest that when no pLOF variants or large deletions are discovered in exonic regions despite strong clinical suspicion, intron sequencing and splicing analysis should be performed.
Topics: Male; Female; Humans; Sertoli-Leydig Cell Tumor; Ovarian Neoplasms; Introns; Germ-Line Mutation; Mutation; Ribonuclease III; DEAD-box RNA Helicases
PubMed: 37883719
DOI: 10.1200/PO.23.00189 -
Indian Journal of Thoracic and... Oct 2019Pleuropulmonary blastoma (PPB) is a rare, malignant tumor of the lung and is the most common primary pulmonary malignancy in children. Here, we report a case of a boy...
Pleuropulmonary blastoma (PPB) is a rare, malignant tumor of the lung and is the most common primary pulmonary malignancy in children. Here, we report a case of a boy who was diagnosed with type I regressed PPB after being mislabeled with congenital pulmonary malformation. A 10-year-old boy presented to our hospital with a history of worsening dyspnea. Since birth, his clinical status and radiographic images were concerning for congenital lobar emphysema that was managed conservatively. A chest computed tomography (CT) scan confirmed the persistence of a large cystic lesion and a diagnostic and therapeutic cystectomy was performed. Microscopic examination confirmed the presence of PPB type Ir. Patient was managed surgically alone with no added chemotherapy, as there was no overall survival benefit. PPB Ir has an overall favorable clinical outcome. Limited follow-up data are available due to the rarity of the lesion and the overlap with other congenital cystic lung malformations.
PubMed: 33061055
DOI: 10.1007/s12055-019-00814-1 -
Journal of Clinical Oncology : Official... Mar 2019DICER1 syndrome is an autosomal-dominant, pleiotropic tumor-predisposition disorder caused by pathogenic germline variants in DICER1. We sought to quantify risk, hazard... (Clinical Trial)
Clinical Trial Observational Study
PURPOSE
DICER1 syndrome is an autosomal-dominant, pleiotropic tumor-predisposition disorder caused by pathogenic germline variants in DICER1. We sought to quantify risk, hazard rates, and the probability of neoplasm incidence accounting for competing risks ("cumulative incidence") of neoplasms (benign and malignant) and standardized incidence ratios for malignant tumors in individuals with DICER1 pathogenic variation.
PATIENTS AND METHODS
We combined data from three large cohorts of patients who carry germline pathogenic variation in DICER1. To reduce ascertainment bias, we distinguished probands from nonprobands. Neoplasm diagnoses were confirmed by review of pathology reports and/or central review of surgical pathology materials. Standardized cancer incidence ratios were determined relative to the SEER program, which does not capture all DICER1-associated neoplasms. For all malignancies and benign tumors ("neoplasms," excluding type Ir pleuropulmonary blastoma and thyroid nodules), we used the Kaplan-Meier method and nonparametric cumulative incidence curves to estimate neoplasm-free survival.
RESULTS
We calculated the age at first neoplasm diagnosis (systematically ascertained cancers plus DICER1-associated neoplasms pleuropulmonary blastoma, cystic nephroma, and nasal chondromesenchymal hamartoma) in 102 female and male nonproband DICER1 carriers. By age 10 years, 5.3% (95% CI, 0.6% to 9.7%) of nonproband DICER1 carriers had developed a neoplasm (females, 4.0%; males, 6.6%). By age 50 years, 19.3% (95% CI, 8.4% to 29.0%) of nonprobands had developed a neoplasm (females, 26.5%; males, 10.2%). After age 10 years, female risk was elevated compared with male risk. Standardized cancer incidence ratio analysis of 102 nonproband DICER1 carriers, which represented 3,344 person-years of observation, showed significant cancer excesses overall, particularly of gynecologic and thyroid cancers.
CONCLUSION
This work provides the first quantitative analysis of site-specific neoplasm risk and excess malignancy risk in 102 systematically characterized nonproband DICER1 carriers. Our findings inform DICER1 syndrome phenotype, natural history, and genetic counseling.
Topics: Adolescent; Adult; Child; Cohort Studies; DEAD-box RNA Helicases; Female; Genetic Predisposition to Disease; Genotype; Germ-Line Mutation; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Pulmonary Blastoma; Registries; Ribonuclease III; Risk Factors; Young Adult
PubMed: 30715996
DOI: 10.1200/JCO.2018.78.4678 -
Modern Pathology : An Official Journal... Jan 2020DICER1 syndrome is a hereditary cancer predisposition syndrome caused by deleterious germline DICER1 mutations. Characteristic "hotspot" somatic mutations of DICER1 have...
DICER1 syndrome is a hereditary cancer predisposition syndrome caused by deleterious germline DICER1 mutations. Characteristic "hotspot" somatic mutations of DICER1 have been identified in DICER1-associated tumors. With the exception of genitourinary embryonal rhabdomyosarcoma and anaplastic sarcoma of the kidney, sarcomas are rarely reported in DICER1 syndrome. Herein, we report the clinical, histopathologic, and molecular findings of a germline DICER1-associated ovarian sarcoma in a 5-year-old female, a somatic DICER1-associated metastatic peritoneal sarcoma in a 16-year-old female, and a somatic DICER1-associated primary intracranial sarcoma in a 4-year-old male. A comprehensive review of the literature, including 83 DICER1-associated sarcomas, illustrates an unequivocal histologic pattern mimicking pleuropulmonary blastoma, regardless of the site of origin. The features include undifferentiated small round blue cells, poorly differentiated spindle cells, and large bizarre pleomorphic cells (anaplasia), often with rhabdomyoblastic and/or chondroid differentiation, and rare bone/osteoid formation. This unique heterogeneous histologic pattern should raise suspicion for pathogenic DICER1 mutation(s) warranting a detailed review of the family history and DICER1 mutation analysis. In addition to expanding the phenotypic spectrum of DICER1-associated conditions, identification of pathogenic DICER1 variants facilitates optimized genetic counseling, caregiver education and judicious imaging-based surveillance.
Topics: Adolescent; Brain Neoplasms; Child, Preschool; DEAD-box RNA Helicases; Female; Genetic Predisposition to Disease; Humans; Male; Mutation; Ovarian Neoplasms; Peritoneal Neoplasms; Ribonuclease III; Sarcoma
PubMed: 31537896
DOI: 10.1038/s41379-019-0366-x -
Missouri Medicine 2019Pleuropulmonary blastoma (PPB), the most common primary malignant neoplasm of the lung in childhood, occurs in the same early age group (0-6 years) as the other more...
Pleuropulmonary blastoma (PPB), the most common primary malignant neoplasm of the lung in childhood, occurs in the same early age group (0-6 years) as the other more common solid tumors such as neuroblastoma and Wilms tumor. The tumor begins as a cystic lung lesion with the potential over a period of 3-5 years to progress to a high grade multipatterned primitive sarcoma in the absence of a malignant epithelial component. Several years after its initial description as a unique clinicopathologic entity, this and other tumors appeared to have a familial predilection which was later confirmed with the discovery of a heterozygous germline mutation in DICER1 whose protein is a member of ribonuclease III family of enzymes. It is estimated that 75%-80% of children with a PPB have the germline mutation. The other notable finding from our studies is the identification of a family of extrapulmonary neoplasms, including cystic nephroma and Sertoli-Leydig cell tumor of the ovary as two examples, also with DICER1 mutations.
Topics: Child; Child, Preschool; DEAD-box RNA Helicases; Female; Germ-Line Mutation; Humans; Infant; Infant, Newborn; Lung Neoplasms; Male; Pulmonary Blastoma; Ribonuclease III
PubMed: 31527943
DOI: No ID Found