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Radiology Case Reports Sep 2021Pleuropulmonary blastoma (PPB) is a rare but aggressive pediatric tumor originates from either lung or pleura. It was recently linked to the DICER I mutation as a part...
Pleuropulmonary blastoma (PPB) is a rare but aggressive pediatric tumor originates from either lung or pleura. It was recently linked to the DICER I mutation as a part of predisposition syndrome for different type of tumor. It is characterized histologically by a primitive, variably mixed blastomatous and sarcomatous tissue. PPB is classified into four subtypes: cystic (type I and type Ir); cystic and solid (type II); solid (type III). PPB has no characteristic imaging findings. Integrated imaging can help to make a differential diagnosis and to recognize the subtypes in order to set up therapy. An early recognition and differentiation from congenital airway malformations and other benign cysts are very important. The treatment consists in a multimodal therapy including surgery and chemoterapy. We report a case of 3 years old female admitted at our hospital with fever, non productive cough and dyspnea, who was diagnosed with type II PPB.
PubMed: 34345335
DOI: 10.1016/j.radcr.2021.06.022 -
Familial Cancer Oct 2023Pathogenic germline DICER1 variants are associated with pleuropulmonary blastoma, multinodular goiter, embryonal rhabdomyosarcoma and other tumour types, while mosaic...
Pathogenic germline DICER1 variants are associated with pleuropulmonary blastoma, multinodular goiter, embryonal rhabdomyosarcoma and other tumour types, while mosaic missense DICER1 variants in the RNase IIIb domain are linked to cause GLOW (global developmental delay, lung cysts, overgrowth, and Wilms' tumor) syndrome. Here, we report four families with germline DICER1 pathogenic variants in which one member in each family had a more complex phenotype, including skeletal findings, facial dysmorphism and developmental abnormalities. The developmental features occur with a variable expressivity and incomplete penetrance as also described for the neoplastic and dysplastic lesions associated with DICER1 variants. Whole exome sequencing (WES) was performed on all four cases and revealed no further pathogenic or likely pathogenic dominant, homozygous or compound heterozygous variants in three of them. Notably, a frameshift variant in ARID1B was detected in one patient explaining part of her phenotype. This series of patients shows that pathogenic DICER1 variants may be associated with a broader phenotypic spectrum than initially assumed, including predisposition to different tumours, skeletal findings, dysmorphism and developmental abnormalities, but genetic work up in syndromic patients should be comprehensive in order not to miss additional underlying /modifying causes.
Topics: Female; Humans; Germ-Line Mutation; Phenotype; Frameshift Mutation; Cysts; Ribonuclease III; Germ Cells; DEAD-box RNA Helicases
PubMed: 34331184
DOI: 10.1007/s10689-021-00271-z -
Head and Neck Pathology Jun 2022DICER1, a member of the ribonuclease III family, is involved in the biogenesis of microRNAs and, hence, it influences gene expression regulation. DICER1 germline...
DICER1, a member of the ribonuclease III family, is involved in the biogenesis of microRNAs and, hence, it influences gene expression regulation. DICER1 germline (associated with the inherited DICER1 syndrome) or somatic mutations have been linked to tumorigenesis in histogenetically diverse benign and malignant neoplasms in different organs including pleuropulmonary blastoma, cystic nephroma, embryonal rhabdomyosarcoma, nasal chondromesenchymal hamartoma, poorly differentiated thyroid carcinoma, thyroblastoma, intracranial sarcoma and gonadal Sertoli-Leydig cell tumors in addition to others. Moreover, rare botryoid (giant) fibroepithelial polyps may harbor this mutation. Herein, we describe the first reported case of a DICER1-mutated botryoid fibroepithelial polyp occurring within the parotid duct of a 65-year-old female who has no other features or family history of the DICER1 syndrome. Based on its distinctive morphology, we tested this lesion specifically for DICER1 mutations and confirmed the presence of a pathogenic DICER1 variant with a low allele frequency, consistent with a somatic mutation.
Topics: Aged; DEAD-box RNA Helicases; Female; Germ-Line Mutation; Humans; Mutation; Neoplastic Syndromes, Hereditary; Polyps; Pulmonary Blastoma; Rare Diseases; Rhabdomyosarcoma, Embryonal; Ribonuclease III; Skin Neoplasms
PubMed: 34282560
DOI: 10.1007/s12105-021-01364-y -
Pediatric and Developmental Pathology :... 2021Pleuropulmonary blastoma (PPB), a rare childhood neoplasm of the lung, is linked to pathogenic variants. We investigated checkpoint inhibitor markers including...
INTRODUCTION
Pleuropulmonary blastoma (PPB), a rare childhood neoplasm of the lung, is linked to pathogenic variants. We investigated checkpoint inhibitor markers including Programmed Death Ligand 1 (PD-L1), PD1, CD8 and tumor mutational burden (TMB) in PPB.
MATERIAL AND METHODS
Cases were collected from departmental archives and the International PPB/ Registry. Immunohistochemistry (IHC) for PD-L1, PD-1, CD8 and DNA mismatch repair (MMR) genes were performed. In addition, normal-tumor paired whole exome sequencing (WES) was performed in two cases.
RESULTS
Twenty-five PPB cases were studied, consisting of Type I (n = 8, including 2 Ir), Type II (n = 8) and Type III (n = 9). PD-L1 combined positive score (CPS) of 1, 4 and 80 was seen in three (3/25, 12.0%) cases of Type II PPB with negative staining in the remaining cases. PD-1 and CD8 stains demonstrated positive correlation ( < .05). The density of PD1 and CD8 in the interface area was higher than within tumor ( < .05). The MMR proteins were retained. TMB was 0.65 mutations/Mb in type II PPB with high expression of PD-L1, and 0.94 mutations/Mb in one negative PD-L1 case with metastatic tumor.
CONCLUSION
A small subpopulation of PPB patient might benefit from checkpoint immunotherapy due to positive PD-L1 staining.
Topics: B7-H1 Antigen; Biomarkers, Tumor; Child; DEAD-box RNA Helicases; Humans; Lung Neoplasms; Mutation; Pulmonary Blastoma; Ribonuclease III
PubMed: 34266329
DOI: 10.1177/10935266211027417 -
Frontiers in Oncology 2021The treatment of asymptomatic patients with congenital pulmonary malformations (CPMs) remains controversial, partially because the relationship between congenital lung...
BACKGROUND AND OBJECTIVES
The treatment of asymptomatic patients with congenital pulmonary malformations (CPMs) remains controversial, partially because the relationship between congenital lung malformations and malignancy is still undefined. Change in methylation pattern is a crucial event in human cancer, including lung cancer. We therefore studied all differentially methylated regions (DMRs) in a series of CPMs in an attempt to find methylation anomalies in genes already described in association with malignancy.
METHODS
The DNA extracted from resected congenital lung malformations and control lung tissue was screened using Illumina MethylationEPIC arrays. Comparisons between the group of malformed samples or the malformed samples of same histology or each malformed sample and the controls and between a pleuropulmonary blastoma (PPB) and controls were performed. Moreover, each malformed sample was pairwise compared with its respective control. All differentially methylated regions (DMRs) with an adjusted p-value <0,05 were studied.
RESULTS
Every comparison highlighted a number of DMRs closed to genes involved either in cell proliferation or in embryonic development or included in the Cancer Gene Census. Their abnormal methylation had been already described in lung tumors.
CONCLUSIONS
Methylation anomalies already described in lung tumors and also shared by the PPB were found in congenital lung malformations, regardless the histology. The presence of methylation abnormalities is suggestive of a correlation between congenital lung malformations and some step of malignant transformation.
PubMed: 34262872
DOI: 10.3389/fonc.2021.689833 -
European Thyroid Journal Jun 2021With the use of ultrasonography for the evaluation of thyroid and nonthyroid neck diseases, the incidental discovery of previously unsuspected thyroid...
INTRODUCTION
With the use of ultrasonography for the evaluation of thyroid and nonthyroid neck diseases, the incidental discovery of previously unsuspected thyroid nodules/nonpalpable lesions has increased. Intrathyroidal thymus arises due to aberrant thymic migration during embryogenesis. It is thought to be rare, fulfils the classiccriteria for diagnosis of an incidentaloma and it can be mistaken for a thyroid nodule. Multinodular goiter is the main endocrine manifestation of DICER1 syndrome, a tumor predisposition syndrome. Careful thyroid examination including ultrasound is thus necessary for DICER1 syndrome patients.
CASE REPORT
A 4-year-old prepubertal boy was referred to the pediatric endocrinology department following an earlier diagnosis of pleuropulmonary blastoma (PPB) type III, which is a hallmark component of DICER1 syndrome. The patient underwent surgery followed by chemotherapy. Genetic analysis identified a germline pathogenic variant (c.2062C>T, p.R688*)in the child and in 5 relatives. A second somatic RNase IIIb hotspot mutation(c.5438A>G, p.E1813G) was identified in DNA extracted from the proband's PPB. He had no goiter on clinical examination, but a heterogenous, well-delineated, avascular, solid and hypoechogenic lesion with pseudomicrocalcifications was observed in the right lobe (4.1 × 3.1 × 2.6 mm), suggestive of thyroid neoplasia. Diagnostic work-up and a 3-year follow-up excluded thyroid neoplasia and confirmed the diagnosis of an intrathyroid benign thymic lesion.
DISCUSSION AND CONCLUSION
This case exemplifies that thyroid incidentalomas in DICER1 syndrome patients should be viewed with great suspicion, but that not all thyroid disorders are indeed -related in these patients.
PubMed: 34178712
DOI: 10.1159/000510004 -
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 -
Radiology Case Reports Jul 2021We are presenting a rare case with the simultaneous occurrence of pleuropulmonary blastoma and an intra lobar pulmonary sequestration. Although there have been cases...
We are presenting a rare case with the simultaneous occurrence of pleuropulmonary blastoma and an intra lobar pulmonary sequestration. Although there have been cases reported previously with pleuropulmonary blastoma associated with congenital pulmonary malformations, the association with an intra lobar pulmonary sequestration is very rare. The patient, a female, 6-month-old child arrived at our pediatric service with the clinic of cough, respiratory distress, and fever after being treated for 2 weeks for left lung bronchopneumonia according clinical signs and radiographic description but without clinical improvements. Contrast enhanced CT images showed the simultaneous presence of 2 different lesions in the left lung, a heterogeneous mass in the superior lobe without delineation with mediastinal structure compatible with a pleuropulmonary blastoma and a consolidation in the inferior lobe with bronchogram present and a systemic vessel feeding compatible with an intra lobar pulmonary sequestration, both confirmed by histologic examinations after the surgical intervention. Although it is very rare, the simultaneous presence of these distinct embryogenic lesions may occur and radiologist should be aware as the imaging diagnosis may be very helpful for the further management of the patient.
PubMed: 34007392
DOI: 10.1016/j.radcr.2021.04.040 -
Modern Pathology : An Official Journal... Jun 2021
Topics: DEAD-box RNA Helicases; Humans; Pulmonary Blastoma; Ribonuclease III; Sarcoma
PubMed: 33875804
DOI: 10.1038/s41379-021-00810-0 -
Pediatric Blood & Cancer Jun 2021Pleuropulmonary blastoma (PPB) is a rare cancer occurring mainly during early childhood and often associated with germline DICER1 mutations. It is classified by the...
Pleuropulmonary blastoma (PPB) is a rare cancer occurring mainly during early childhood and often associated with germline DICER1 mutations. It is classified by the macroscopic appearance into three interrelated clinico-pathologic entities on a developmental continuum. Complete tumor resection is a main prognostic factor and can be performed at diagnosis or after neoadjuvant treatment that includes chemotherapy and in some cases radiotherapy. Optimal modalities of neo- or adjuvant treatments can be challenging taking into account potential long-term toxicities in this young population. This paper presents the recommendations for diagnosis and treatment of children and adolescents with PPB elaborated by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) within the European Union-funded project PARTNER (Paediatric Rare Tumours Network - European Registry).
Topics: Adolescent; Child; Child, Preschool; DEAD-box RNA Helicases; Humans; Lung Neoplasms; Neoadjuvant Therapy; Pulmonary Blastoma; Registries; Ribonuclease III
PubMed: 33826235
DOI: 10.1002/pbc.29045