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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 -
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 -
Pediatrics Apr 2021Pediatric lung lesions are a group of mostly benign pulmonary anomalies with a broad spectrum of clinical disease and histopathology. Our objective was to evaluate the...
BACKGROUND
Pediatric lung lesions are a group of mostly benign pulmonary anomalies with a broad spectrum of clinical disease and histopathology. Our objective was to evaluate the characteristics of children undergoing resection of a primary lung lesion and to identify preoperative risk factors for malignancy.
METHODS
A retrospective cohort study was conducted by using an operative database of 521 primary lung lesions managed at 11 children's hospitals in the United States. Multivariable logistic regression was used to examine the relationship between preoperative characteristics and risk of malignancy, including pleuropulmonary blastoma (PPB).
RESULTS
None of the 344 prenatally diagnosed lesions had malignant pathology ( < .0001). Among 177 children without a history of prenatal detection, 15 (8.7%) were classified as having a malignant tumor (type 1 PPB, = 11; other PPB, = 3; adenocarcinoma, = 1) at a median age of 20.7 months (interquartile range, 7.9-58.1). Malignancy was associated with the DICER1 mutation in 8 (57%) PPB cases. No malignant lesion had a systemic feeding vessel ( = .0427). The sensitivity of preoperative chest computed tomography (CT) for detecting malignant pathology was 33.3% (95% confidence interval [CI]: 15.2-58.3). Multivariable logistic regression revealed that increased suspicion of malignancy by CT and bilateral disease were significant predictors of malignant pathology (odds ratios of 42.15 [95% CI, 7.43-340.3; < .0001] and 42.03 [95% CI, 3.51-995.6; = .0041], respectively).
CONCLUSIONS
In pediatric lung masses initially diagnosed after birth, the risk of PPB approached 10%. These results strongly caution against routine nonoperative management in this patient population. DICER1 testing may be helpful given the poor sensitivity of CT for identifying malignant pathology.
Topics: Child, Preschool; Cohort Studies; DEAD-box RNA Helicases; Female; Humans; Infant; Infant, Newborn; Length of Stay; Lung Neoplasms; Mutation; Neoplasm Metastasis; Pregnancy; Prenatal Diagnosis; Pulmonary Blastoma; Respiratory Distress Syndrome, Newborn; Retrospective Studies; Ribonuclease III; Tomography, X-Ray Computed
PubMed: 33762310
DOI: 10.1542/peds.2020-028357 -
Pediatric Blood & Cancer Jun 2021Limited data are available regarding radiation therapy in pediatric pleuropulmonary blastoma (PPB). We report the case of a 3-year-old girl with type II PPB successfully...
Limited data are available regarding radiation therapy in pediatric pleuropulmonary blastoma (PPB). We report the case of a 3-year-old girl with type II PPB successfully treated with trimodality therapy including multiagent chemotherapy, resection, and whole pleura radiation therapy. While longer follow-up is required to confirm ultimate local tumor control and long-term post-treatment sequelae, currently 3.5 years following therapy, she is well, without recurrent disease or observable toxicity. The goal of this report is to add our experience to the literature regarding PPB, its management, and treatment, as prospective randomized controlled trials are not feasible due to the rarity of this disease.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Child, Preschool; Combined Modality Therapy; DEAD-box RNA Helicases; Dactinomycin; Doxorubicin; Female; Frameshift Mutation; Humans; Ifosfamide; Lung Neoplasms; Pulmonary Blastoma; Radiotherapy, Conformal; Ribonuclease III; Vincristine
PubMed: 33751747
DOI: 10.1002/pbc.29004 -
Lung India : Official Organ of Indian... 2021Fetal lung interstitial tumor (FLIT) is a rare pediatric lung tumor with radiological features similar to developmental pulmonary malformations and other congenital lung...
Fetal lung interstitial tumor (FLIT) is a rare pediatric lung tumor with radiological features similar to developmental pulmonary malformations and other congenital lung neoplasms. There are about 17 cases of FLIT reported worldwide till date. We report the first case of FLIT in the Indian literature which was diagnosed in the early postnatal period (at the 21 day of life) by pathological examination. The tumor exhibited a novel focal micropapillary architecture, in addition to the previously described microscopic features. We discuss the pathogenesis and differential diagnoses of FLIT and review the literature.
PubMed: 33687015
DOI: 10.4103/lungindia.lungindia_646_20