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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 -
Radiology Case Reports Sep 2022Pleuropulmonary blastoma (PPB) is among the rarest malignant tumors diagnosed in children. PPBs can be histopathologically classified into 3 types: cystic tumor (type...
Pleuropulmonary blastoma (PPB) is among the rarest malignant tumors diagnosed in children. PPBs can be histopathologically classified into 3 types: cystic tumor (type I), mixed cystic and solid tumor (type II), and pure solid tumor (type III). We describe a case of type III PPB that was detected in a prenatal fetus, confirmed using histopathological methods. To the best of our knowledge, this is the first case describing a type III PPB detected in a fetus. Prenatal ultrasonography is an excellent tool for detecting pulmonary lesions during the diagnostic phase, and the possibility of PPB should be considered when solid tumors are detected. Early detection can allow for the performance of full resection, leading to a better prognosis for this cancerous tumor.
PubMed: 35818452
DOI: 10.1016/j.radcr.2022.06.032 -
Radiology Case Reports Oct 2023Congenital pulmonary airway malformation (CPAM) is a rare congenital dysplastic malformation characterized by failure of bronchial development and localized glandular...
Congenital pulmonary airway malformation (CPAM) is a rare congenital dysplastic malformation characterized by failure of bronchial development and localized glandular overgrowth. Previously known as Congenital Cystic Adenoid Malformation (CCAM), CPAM is classified into 5 types, from type 0 to type IV, depending upon the origin of pulmonary areas of the lung, cyst size, and cyst appearance. CPAM is a rare congenital anomaly typically diagnosed prenatally in ultrasound. However, few cases are diagnosed in childhood and even fewer in adulthood. CPAM can be differentiated from pulmonary sequestration based on the origin of the arterial supply; the former has its arterial supply from the pulmonary artery, whereas pulmonary sequestration has its arterial supply from the systemic circulation. Another differential diagnosis of CPAM includes congenital bronchogenic cyst, congenital lobar emphysema, pleuropulmonary blastoma, congenital cystic bronchiectasis, and congenital diaphragmatic hernia. The most common presentation is recurrent chest infection and chest pain, whereas other presentation includes pneumothorax and hemoptysis. Here, we present a case of a 6-year-old child with recurrent episodes of fever and cough diagnosed as a type II CPAM based on computed tomography findings.
PubMed: 37539443
DOI: 10.1016/j.radcr.2023.07.018 -
International Journal of Clinical and... 2015In infants, pleuropulmonary blastoma is a rare but aggressive tumor. The typical histopathological presentation includes the aggregation of malignant primitive small...
In infants, pleuropulmonary blastoma is a rare but aggressive tumor. The typical histopathological presentation includes the aggregation of malignant primitive small cells, usually observed in sheets. So as to provide proper and timely treatment, the differential diagnosis includes pulmonary blastoma, sarcomatoid mesothelioma, fetal rhabdomyoma, synovial sarcoma, and primitive neuroectodermal tumor. Herein, we will present one male pediatric patient with pleuropulmonary blastoma. The patient was a 4-month-old male infant, who had a prolonged cough and dyspnea for 4 months that was complicated by cyanosis for 3 days. A physical examination revealed a solid mass in the right lung that was sized 9.0 × 6.0 × 4.0 cm and had a grayish-white cross section. The boundary between the mass and lung tissue was clear; the mass already occupied a great portion of the lung. A microscopic examination suggested that the tumor was composed of round or orbicular-ovate primitive fetal cells. The cells were medium sized, having little cytoplasm, but had a clearly visualized nucleolus and active karyokinesis. The tumor mass was biphasic, namely, fasciculated sarcoma (composed of spindle-shaped cells and short spindle-shaped cells) and malignant fibrous histiocytoma containing well-differentiated cartilage islands or cartilaginous nodes. Immunohistochemistry was performed for further detection: vimentin (+), S-100 protein (+), CK (AE1/AE3), EMA and TTF-1 in residual epithelial components (+), NSE (focal +), SMA (mesenchymal cells, focal +), CD99 (weak +), Bcl-2 (weak +), desmin (-), myoglobin (-), calretinin (-), calponin (-), FLI (-), MyoD-1 (-), and CD34 (-). Pleuropulmonary blastoma is extremely rare but highly aggressive neoplasm in children. Its typical histopathological presentation is the aggregation of primitive malignant small cells. Combining imaging and histopathological examinations and clinical data should help in determining the diagnosis of pleural pulmonary blastoma.
Topics: Biomarkers, Tumor; Humans; Infant; Lung; Lung Neoplasms; Male; Pulmonary Blastoma
PubMed: 26722577
DOI: No ID Found -
Indian Journal of Ophthalmology Jun 2019Intraocular medulloepithelioma is a nonhereditary neoplasm of childhood arising from primitive medullary epithelium. It most often involves the ciliary body. Most... (Review)
Review
Intraocular medulloepithelioma is a nonhereditary neoplasm of childhood arising from primitive medullary epithelium. It most often involves the ciliary body. Most patients present between 2 and 10 years of age with loss of vision, pain, leucocoria, or conjunctival congestion. The mass appears as a grey-white ciliary body lesion with intratumoral cysts. Presence of a neoplastic cyclitic membrane with extension to retrolental region is characteristic. Secondary manifestations like cataract and neovascular glaucoma may be present in up to 50% and 60% patients, respectively. These could be the first signs for which, unfortunately, about 50% patients undergo surgery before recognition of the hidden tumor. Systemic correlation with pleuropulmonary blastoma (DICER1 gene) has been documented in 5% cases. Histopathology shows primitive neuroepithelial cells arranged as cords closely resembling the primitive retina. Histopathologically, the tumor is classified as teratoid (containing heteroplastic elements) and nonteratoid (containing medullary epithelial elements), each of which are further subclassified as benign or malignant. Retinoblastoma-like and sarcoma-like areas may be seen within the tissue. The treatment modality depends on tumor size and extent of invasion. For small localized tumors (≤3-4 clock hours), conservative treatments with cryotherapy, plaque radiotherapy, or partial lamellar sclerouvectomy (PLSU) have been used. Plaque brachytherapy is generally preferred for best tumor control. Advanced and extensive tumors require enucleation. Rare use of intra-arterial and intravitreal chemotherapy has been employed. Systemic prognosis is favorable, but those with extraocular extension and orbital involvement show risk for local recurrence and metastatic disease, which can lead to death.
Topics: Combined Modality Therapy; DEAD-box RNA Helicases; DNA, Neoplasm; Disease Management; Eye Neoplasms; Humans; Mutation; Neuroectodermal Tumors, Primitive; Ribonuclease III
PubMed: 31124483
DOI: 10.4103/ijo.IJO_845_19 -
International Journal of Surgery Case... May 2023Pleuropulmonary blastoma (PPB) is rare, representing 0.3 % of all pediatric cancers. PPB is classified into three subtypes and may progress from type I to types II and...
INTRODUCTION
Pleuropulmonary blastoma (PPB) is rare, representing 0.3 % of all pediatric cancers. PPB is classified into three subtypes and may progress from type I to types II and III, with a worse prognosis. Given its rarity, the diagnosis is frequently challenging.
CASE PRESENTATION
We report an occurrence of PPB in a 3-year-old girl, who presented recurrent pneumopathy. Imaging investigations revealed a large solid lesion in the left hemithorax. Biopsy followed by histological analysis suggested rhabdomyosarcoma. The patient received neoadjuvant chemotherapy before proceeding to complete tumor excision. Surgical exploration revealed that the tumor was primitively related to parietal pleura and lower lobe of left lung. Histopathology of the tumor retained a definitive diagnosis of PPB type II. Postoperative course was uneventful, and a cerebral MRI ruled out brain metastasis. Adjuvant chemotherapy was administered.
DISCUSSION
Clinical expression of PPB is nonspecific and variable. It ranges from a dry cough to respiratory distress. Standard radiography is the first examination to perform and CT is the gold standard for characterization thoracic masses. Surgery and chemotherapy are the pillars of treatment. Indications depend on the tumor type, its extent and its resectability.
CONCLUSION
PPB is an aggressive tumor that occurs only in children. Due to the rarity of PPB, evidence on optimal treatment is still insufficient. Careful follow-up is necessary searching for local recurrence or metastasis.
PubMed: 37119756
DOI: 10.1016/j.ijscr.2023.108261 -
The Journal of Pathology May 2015Inherited syndromes provide unique opportunities to identify key regulatory mechanisms governing human disease. We previously identified germline loss-of-function DICER1...
Inherited syndromes provide unique opportunities to identify key regulatory mechanisms governing human disease. We previously identified germline loss-of-function DICER1 mutations in a human syndrome defined by the childhood lung neoplasm pleuropulmonary blastoma (PPB), which arises during lung development. DICER1 regulates many biological processes critical in development and disease pathogenesis. Significant challenges in defining the role of DICER1 in human disease are identifying cause-effect relationships and generating manipulatable systems that model the complexity of organ development and disease pathogenesis. Here we report the generation of a murine model for PPB and demonstrate that precise temporal and cell type-specific Dicer1 ablation is necessary and sufficient for the development of cystic lungs that histologically and phenotypically model PPB. Dicer1 ablation in the distal airway epithelium during early stages of lung development resulted in a cystic lung phenotype indistinguishable from PPB, whereas DICER1 function was not required for development of the proximal airway epithelium or during later stages of organogenesis. Mechanistic studies demonstrate that Dicer1 loss results in epithelial cell death, followed by cystic airway dilatation accompanied by epithelial and mesenchymal proliferation. These studies define precise temporal and epithelial cell type-specific DICER1 functions in the developing lung and demonstrate that loss of these DICER1 functions is sufficient for the development of cystic PPB. These results also provide evidence that PPB arise through a novel mechanism of non-cell-autonomous tumour initiation, in which the genetic abnormality initiating the neoplasm does not occur in the cells that ultimately transform, but rather occurs in a benign-appearing epithelial cell component that predisposes underlying mesenchymal cells to malignant transformation.
Topics: Animals; DEAD-box RNA Helicases; Disease Models, Animal; Epithelium; Germ-Line Mutation; Humans; Lung Neoplasms; Mice; Pulmonary Blastoma; Ribonuclease III
PubMed: 25500911
DOI: 10.1002/path.4500 -
Journal of Thoracic Oncology : Official... Nov 2016The appropriate management of asymptomatic congenital pulmonary malformations (CPMs) remains controversial. Prophylactic surgery is recommended to avoid the risk for... (Review)
Review
INTRODUCTION
The appropriate management of asymptomatic congenital pulmonary malformations (CPMs) remains controversial. Prophylactic surgery is recommended to avoid the risk for development of pulmonary infections and to prevent the highly debated development of malignancy. However, the true risk for development of malignancy remains unknown. A systematic review analyzed all cases in which lung tumors associated with CPMs in both the pediatric and adult populations were described.
METHODS
A comprehensive literature search was carried out; it included all the cases in which an association between CPMs and malignant pulmonary lesions was reported.
RESULTS
In all, 134 publications were eligible for inclusion. In 168 patients CPM was found associated with lung tumor. The diagnosis was made in 76 children at a mean age of 3.68 ± 3.4, whereas in the adult population (n = 92) it was made at a mean age of 44.62 ± 16.09. Cough was the most frequent presenting symptom both in children and in adults. Most of the patients underwent lobectomy. The tumor most often associated with CPM was pleuropulmonary bastoma in children (n = 31) and adenocarcinoma (n = 20) or bronchioloalveolar carcinoma (n = 20) in adults. The CPM most frequenty associated with tumors in children was congenital cystic adenomatoid malformation (n = 37), especially type 1 (n = 21), whereas in adults it was bronchogenic cyst (n = 25), followed by congenital cystic adenomatoid malformation (n = 21).
CONCLUSIONS
CPMs should be followed up and never underestimated because they may conceal a tumor. Apparently, there is no age limit for malignant progression of CPMs and no limit of the interval between first detection of the CPM and appearance of the associated tumor.
Topics: Adenocarcinoma; Adult; Child, Preschool; Congenital Abnormalities; Female; Humans; Lung Neoplasms; Male
PubMed: 27423390
DOI: 10.1016/j.jtho.2016.06.023 -
Radiology Case Reports Oct 2021Pleuropulmonary blastoma is a rare, aggressive, malignant tumor of the lungs or pleura that primarily affects children. Pleuropulmonary blastoma is classified into 3...
Pleuropulmonary blastoma is a rare, aggressive, malignant tumor of the lungs or pleura that primarily affects children. Pleuropulmonary blastoma is classified into 3 types based on morphology, including cystic (type I), mixed (type II), or solid (type III). These morphological types correlate with prognosis. In this article, we present a case of type III pleuropulmonary blastoma in a 2-year-old girl. The patient was treated with tumoral resection and chemotherapy; however, she experienced local recurrence and spinal metastasis after 5 months of treatment.
PubMed: 34401036
DOI: 10.1016/j.radcr.2021.07.024 -
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