Type II pleuropulmonary blastoma in a 3-years-old female with dyspnea: a case report and review of literature.
Ontology highlight
ABSTRACT:
SUBMITTER: Ferrara D
PROVIDER: S-EPMC8319522 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BACKGROUND:Pleuropulmonary blastoma (PPB) has 3 subtypes on a tumor progression pathway ranging from type I (cystic) to type II (cystic/solid) and type III (completely solid). A germline mutation in DICER1 is the genetic cause in the majority of PPB cases. METHODS:Patients confirmed to have PPB by central pathology review were included, and their clinical characteristics and outcomes were reported. Germline DICER1 mutations were sought with Sanger sequencing. RESULTS:There were 435 cases, and a central review confirmed 350 cases to be PPB; 85 cases (20%) were another entity. Thirty-three percent of the 350 PPB cases were type I or type I regressed (type Ir), 35% were type II, and 32% were type III or type II/III. The median ages at diagnosis for type I, type II, and type III patients were 8, 35, and 41 months, respectively. The 5-year overall survival (OS) rate for type I/Ir patients was 91%; all deaths in this group were due to progression to type II or III. OS was significantly better for type II versus type III (P?=?.0061); the 5-year OS rates were 71% and 53%, respectively. Disease-free survival (DFS) was also significantly better for type II versus type III (P?=?.0002); the 5-year DFS rates were 59% and 37%, respectively. The PPB type was the strongest predictor of outcome. Metastatic disease at the diagnosis of types II and III was also an independent unfavorable prognostic factor. Sixty-six percent of the 97 patients tested had a heterozygous germline DICER1 mutation. In this subset, the DICER1 germline mutation status was not related to the outcome. CONCLUSIONS:Cystic type I/Ir PPB has a better prognosis than type II, and type II has a better outcome than type III. Surveillance of DICER1 carriers may allow the earlier detection of cystic PPB before its progression to type II or III PPB and thereby improve outcomes.
| S-EPMC4293209 | biostudies-literature
Project description:Pleuropulmonary blastoma (PPB) is a childhood cancer arising from pleuropulmonary mesenchyme. This neoplasm is a sentinel disease in a familial tumor syndrome recently found to be associated with germline mutations in DICER1. Observations of ovarian sex cord-stromal tumors (OSCST) in PPB kindreds led to further study. We sought to characterize ovarian tumors seen in probands and families with PPB and PPB-related conditions and define germline DICER1 status.Patient and family records of pathology-reviewed PPB cases enrolled in the International PPB Registry (IPPBR) were searched for ovarian tumors. Ovarian tumor pathology specimens were obtained and centrally reviewed. Germline DNA from patients with ovarian tumors was tested for DICER1 mutations. Three additional OSCST patients registered in the IPPBR were also tested for mutations in DICER1.Among 296 kindreds including 325 children with PPB, we observed three children with both PPB and Sertoli-Leydig cell tumors (SLCT)/Sertoli cell tumors. Among family members of PPB patients, we identified six OSCST (three SLCT, one Sertoli cell tumor, one juvenile granulosa cell tumor, one gynandroblastoma). Age at ovarian tumor diagnosis was youngest in PPB probands and younger in family members than in OSCST in general. Germline DICER1 mutations were identified in four of six patients with OSCST from PPB kindreds and in two of three children with OSCST and no personal or family history of PPB.Primary ovarian neoplasms, particularly OSCST, are a manifestation of the familial PPB syndrome and may be the initial clinical presentation of DICER1 mutations within a family.
| S-EPMC3138876 | biostudies-literature
Project description:Pleuropulmonary blastoma (PPB) is a rare pediatric lung tumor that is often part of an inherited cancer syndrome. PPBs consist of mesenchymal cells that are susceptible to malignant transformation and cysts lined by epithelial cells. In a subset of patients, overgrowth of the cysts by mesenchymal cells leads to sarcoma formation. Here, we show that 11 multiplex PPB families harbor heterozygous germline mutations in DICER1, a gene encoding an endoribonuclease critical to the generation of small noncoding regulatory RNAs. Expression of DICER1 protein was undetectable in the epithelial component of PPB tumors but was retained in the malignant mesenchyme (sarcoma). We hypothesize that loss of DICER1 in the epithelium of the developing lung alters the regulation of diffusible factors that promote mesenchymal proliferation.
| S-EPMC3098036 | biostudies-literature
Project description:IntroductionTuberous sclerosis complex (TSC) is an uncommon multisystem disorder that can affect the lungs, skin, kidneys, and brain. The study highlights the importance of genetic and clinical diagnostic criteria in identifying this rare condition and the role of surveillance in preventing complications.Case presentationHerein, we report a case of 16 years old female presenting with right flank pain, hematuria, hypopigmented macule over the back, ash leaf spots over the right upper and lower limb, and a palpable mass over the right lumbar region. Laboratory tests showed low hemoglobin with plenty of red blood cells in urine. She was admitted for symptomatic management of pain and blood transfusion was done to manage anemia. After a diagnostic workup for tuberous sclerosis, she was diagnosed with the condition and is under regular follow-up.Clinical discussionTuberous sclerosis complex is one of the neurocutaneous syndromes, diagnosed based on the genetic or clinical diagnostic criteria as per the second International Tuberous Sclerosis Complex Consensus Conference 2012, which have been updated in 2021 with no changes in genetic diagnostic criteria and slight changes in clinical diagnostic criteria. After diagnosis, along with the management, surveillance is also crucial.ConclusionTuberous sclerosis runs a progressive course and can lead to various complications. Thus, early diagnosis with the help of genetic and clinical diagnostic criteria is important along with regular surveillance of different body systems to prevent debilitating complications.
| S-EPMC8844758 | biostudies-literature
Project description:Introduction and importance In its complex way of embryonic evolvement, the diaphragmatic membrane can be involved with various disorders that may partially or entirely not develop. Agenesis of the diaphragm is the term that refers to this maldevelopment. It is the more severe form of congenital diaphragmatic hernia in which intra-abdominal viscera protrude into the thoracic cavity, causing respiratory and gastrointestinal problems. Most neonates delivered with diaphragmatic agenesis do not live more than hours to days of the severity of lung immaturity. However, less than 20 affected cases have been reported so far that survived to childhood and even their adulthood period treated surgically or conservatively. We have reported a case of neglected left hemi-diaphragmatic agenesis for more than six decades, then reviewed all adult diaphragmatic agenesis cases available in the literature for 74 years. Case presentation A 65-year-old female complaining of worsened dyspnea during the last four months, a chronic history of short breath since her fourth decade of life, and recent surgery with the diagnosis of a diaphragmatic hernia, underwent the thoracotomy twice in which unilateral diaphragmatic hernia was diagnosed then repaired. Clinical discussion For the recurrence of her symptoms, she underwent a second thoracotomy, in which the final diagnosis of left hemi-diaphragmatic agenesis was made. A dual mesh patch constructed the defect. The post-operation period was uneventful. We only found 17 cases of adult hemi or bilateral agenesis of the diaphragm reviewing the main medical literature such as Medline and Web of Science. The conservative and operative treatment managements were equal for eight patients in each of them. One of them refused therapy, and one was non-declared in the study. As in congenital diaphragmatic hernia, the most typical side was the left in 10 out of 18. The most complaints patients had followed by coughing and bowel obstruction was dyspnea and dyspepsia. Conclusion Near the total of the diaphragmatic agenesis cases die in the neonatal population; remained undiagnosed or during an autopsy found. However, typically rare in the adult population, respiratory and digestive disorders are the most prevalent. It is difficult initially because diagnosing is intraoperatively, and no modality is available to help the examiner physician diagnose perinatally. Graphical abstract Image 1 Highlights • Diaphragmatic agenesis is a rare anomaly seen usually in the neonatal period.• The diagnosis is made during autopsy or surgery.• The most common affected side is the left, and bilateral ageneses are reported only once in the literature.• Who survive are usually not symptomatic until adulthood when bowel obstruction, pneumonia, or shortness of breath occur.• We have only found 18 adult diaphragmatic agenesis cases for 74 years now.
| S-EPMC9793280 | biostudies-literature
Project description:A 29-year old female patient was referred to our hospital for evaluation of dyspnea NYHA class I which begun from several months ago. The only abnormal sign found on physical examination was a grade 2/6 systolic murmur at the apex position without radiation. Echocardiography revealed normal left and right ventricular sizes and systolic function, and only one papillary muscle in left ventricular (LV) cavity which all chordae tendineae inserted into that muscle. The mitral valve orifice was eccentrically located at the lateral side with mild to moderate mitral regurgitation but without significant mitral stenosis. No other congenital heart anomalies were identified. Thus, the final diagnosis was isolated parachute mitral valve (IPMV). She was one of the very rare IPMV cases have ever been reported in adults.
| S-EPMC4827139 | biostudies-literature
Project description:Background and aims:Pneumothoraces can occur in patients of all ages and genders. We encountered a female adolescent patient who was experiencing recurrent pneumothoraces every several months. She endured an extensive workup to determine an etiology for her pneumothoraces but it was all negative. She was eventually diagnosed with catamenial pneumothorax. This is an established cause of recurrent pneumothorax in adults but is very rare in adolescent patients. Keeping it on the differential for any female of reproductive age with recurrent pneumothoraces may prevent potentially harmful and expensive diagnostic testing and procedures. Methods:We reported a case of catamenial pneumothorax in an adolescent patient and reviewed the relevant literature. Results:Our patient was a 14-year-old female patient with recurrent pneumothoraces every several months. She had an extensive procedural and genetic workup performed but no etiology was revealed. Due to a temporal relation of the pneumothoraces to menses, an obstetrics and gynecology consult was obtained. Empirical treatment for catamenial pneumothorax was started with a continuous oral contraceptive with combined estrogen-progestin leading to our patient's complete remission. Three years later our patient has not experienced any relapsing episodes of pneumothorax. Conclusion:Although rare in younger patients, catamenial pneumothorax should be considered as a cause for recurrent pnueumothoraces in any post-pubertal female.
| S-EPMC6831874 | biostudies-literature
Project description:DICER1 is a critical gene in the biogenesis of mature microRNAs, short non-coding RNAs that derive from either -3p or -5p precursor microRNA strands. Germline mutations of DICER1 are associated with a range of human malignancies, including pleuropulmonary blastoma (PPB). Additional somatic 'hotspot' mutations in the microRNA processing ribonuclease IIIb (RNase IIIb) domain of DICER1 are reported in cancer, and which affect microRNA biogenesis, resulting in a -3p mature microRNA strand bias. Here, in a germline (exon11 c.1806_1810insATTGA) DICER1-mutated PPB, we first confirmed the presence of an additional somatic RNase IIIb hotspot mutation (exon25 c.5425G>A [p.G1809R]) by conventional sequencing. Second, we investigated serum levels of mature microRNAs at the time of PPB diagnosis, and compared the findings with serum results from a comprehensive range of pediatric cancer patients and controls (n=52). We identified a panel of 45 microRNAs that were present at elevated levels in the serum at the time of PPB diagnosis, with a significant majority noted be derived from the -3p strand (P=0.013). In addition, we identified a subset of 10 serum microRNAs (namely miR-125a-3p, miR-125b-2-3p, miR-380-5p, miR-125b-1-3p, let-7f-2-3p, let-7a-3p, let-7b-3p, miR-708-3p, miR-138-1-3p and miR-532-3p) that were most abundant in the PPB case. Serum levels of two representative microRNAs, miR-125a-3p and miR-125b-2-3p, were not elevated in DICER1 germline-mutated relatives. In the PPB case, serum levels of miR-125a-3p and miR-125b-2-3p increased before chemotherapy, and then showed an early reduction following treatment. These microRNAs may offer future utility as serum biomarkers for screening patients with known germline DICER1 mutations for early detection of PPB, and for potential disease-monitoring in cases with confirmed PPB.
| S-EPMC3940920 | biostudies-literature
Project description:IntroductionPleuropulmonary blastoma (PPB), a rare childhood neoplasm of the lung, is linked to pathogenic DICER1 variants. We investigated checkpoint inhibitor markers including Programmed Death Ligand 1 (PD-L1), PD1, CD8 and tumor mutational burden (TMB) in PPB.Material and methodsCases were collected from departmental archives and the International PPB/DICER1 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.ResultsTwenty-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 (P < .05). The density of PD1 and CD8 in the interface area was higher than within tumor (P < .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.ConclusionA small subpopulation of PPB patient might benefit from checkpoint immunotherapy due to positive PD-L1 staining.
| S-EPMC9196202 | biostudies-literature
Project description:Pleuropulmonary blastoma (PPB) is a rare pediatric lung neoplasm that recapitulates developmental pathways of early embryonic lungs. As lung development proceeds with highly regulated mesenchymal-epithelial interactions, a DICER1 mutation in PPB generates a faulty lung differentiation program with resultant biphasic tumors composed of a primitive epithelial and mesenchymal stroma with early progenitor blastomatous cells. Deciphering of PPB progression has been hampered by the difficulty of culturing PPB cells, and specifically progenitor blastomatous cells. Here, we show that in contrast with in-vitro culture, establishment of PPB patient-derived xenograft (PDX) in NOD-SCID mice selects for highly proliferating progenitor blastoma overexpressing critical regulators of lung development and multiple imprinted genes. These stem-like tumors were sequentially interrogated by gene profiling to show a FGF module that is activated alongside Neural cell adhesion molecule 1 (NCAM1). Targeting the progenitor blastoma and these transitions with an anti-NCAM1 immunoconjugate (Lorvotuzumab mertansine) inhibited tumor growth and progression providing new paradigms for PPB therapeutics. Altogether, our novel in-vivo PPB xenograft model allowed us to enrich for highly proliferating stem-like cells and to identify FGFR and NCAM1 as two key players that can serve as therapeutic targets in this poorly understood and aggressive disease.
| S-EPMC6718423 | biostudies-literature