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Pediatric Blood & Cancer Nov 2023Pleuropulmonary blastoma (PPB) is the most common primary lung neoplasm of infancy and early childhood. Given the rarity of PPB, the role of positron emission tomography...
Assessing the role of positron emission tomography and bone scintigraphy in imaging of pleuropulmonary blastoma (PPB): A report from the International PPB/DICER1 Registry.
BACKGROUND
Pleuropulmonary blastoma (PPB) is the most common primary lung neoplasm of infancy and early childhood. Given the rarity of PPB, the role of positron emission tomography (PET) and bone scintigraphy (bone scans) in diagnostic evaluation and surveillance has not been documented to date. Available PET and bone scan data are presented in this study.
PROCEDURES
Patients with PPB enrolled in the International PPB/DICER1 Registry and available PET imaging and/or bone scan reports were retrospectively abstracted.
RESULTS
On retrospective analysis, 133 patients with type II and III (advanced) PPB were identified with available report(s) (PET scan only = 34, bone scan only = 83, and both bone scan and PET = 16). All advanced primary PPB (n = 11) and recurrent (n = 8) tumors prior to treatment presented with F-fluorodeoxyglucose (FDG)-avid lesions, with median maximum standardized uptake values of 7.4 and 6.7, respectively. False positive FDG uptake in the thorax was noted during surveillance (specificity: 59%). Bone metastases were FDG-avid prior to treatment. Central nervous system metastases were not discernable on PET imaging. Sensitivity and specificity of bone scans for metastatic bone disease were 89% and 92%, respectively. Bone scans had a negative predictive value of 99%, although positive predictive value was 53%. Four patients with distant bone metastases had concordant true positive bone scan and PET.
CONCLUSION
Primary, recurrent, and/or extracranial metastatic PPB presents with an FDG-avid lesion on PET imaging. Additional prospective studies are needed to fully assess the utility of nuclear medicine imaging in surveillance for patients with advanced PPB.
Topics: Humans; Child, Preschool; Retrospective Studies; Fluorodeoxyglucose F18; Positron-Emission Tomography; Radionuclide Imaging; Sensitivity and Specificity; Bone Neoplasms; Registries; Radiopharmaceuticals; Ribonuclease III; DEAD-box RNA Helicases
PubMed: 37592371
DOI: 10.1002/pbc.30628 -
Children (Basel, Switzerland) Apr 2024Pleuropulmonary blastoma (PPB) is a rare childhood tumor originating from the lung or pleura, typically treated with surgery, chemotherapy (CTx), and/or radiation...
Pleuropulmonary blastoma (PPB) is a rare childhood tumor originating from the lung or pleura, typically treated with surgery, chemotherapy (CTx), and/or radiation therapy (RTx). This study aimed to assess patient and tumor features, treatment methods, and survival rates in PPB. We retrospectively analyzed PPB patients under 18 from 2004 to 2019, using the National Cancer Database (NCDB). We assessed 5-year overall survival (OS) rates based on disease presentation and treatment regimens, using Kaplan-Meier curves and Cox proportional regression. Among 144 cases identified, 45.9% were female, with a median age of 2 years (interquartile range 1-3). In all, 62.5% of tumors originated from the lung, and 10.4% from the pleura. Moreover, 6.9% were bilateral, and the median tumor size was 8.9 cm, with 4.2% presenting with metastases. The 5-year OS rate was 79.6%, with no significant change over time (2004-2009, 77.6%; 2010-2014, 90.8%; 2015-2019, OS 75.3%; = 0.08). In all, 5.6% received CTx alone, 31.3% surgery alone, 45.8% surgery/CTx, and 17.4% surgery/CTx/RTx. The OS rates were comparable between the surgery/CTx/RTx (80.0%) and surgery/CTx (76.5%) groups (adjusted Hazard Ratio, 1.72; 95% CI, 0.57-5.19; = 0.34). Therefore, due to the unchanged survival rates over time, further prospective multicenter studies are needed to determine the optimal multimodal treatment regimens for this rare pediatric tumor.
PubMed: 38671641
DOI: 10.3390/children11040424 -
Archive of Clinical Cases 2024Mediastinal tumors are exceedingly rare during fetal development, presenting significant diagnostic challenges and potentially leading to severe outcomes such as...
Mediastinal tumors are exceedingly rare during fetal development, presenting significant diagnostic challenges and potentially leading to severe outcomes such as stillbirth or metastatic disease if not promptly identified and managed. Pleuropulmonary blastomas are primitive mesenchymal tumors often linked to mutations in the DICER1 gene, indicating a hereditary pattern associated with other common adult neoplasms with dominant inheritance. This report describes a case involving a 20-year-old Caucasian woman whose pregnancy was complicated by a stillbirth in the second trimester. Initial suspicions of a mediastinal tumor arose from blood tests and ultrasound examinations during pregnancy surveillance. However, the definitive diagnosis of a type II pleuropulmonary blastoma was established through a pathological examination at autopsy. This case underscores the complexities of diagnosing fetal mediastinal tumors and contributes to the sparse literature on neonatal pleuropulmonary blastomas. Our comprehensive review of the differential diagnoses and literature emphasizes the unique characteristics of pleuropulmonary blastoma and its similarities to other soft tissue sarcomas, enhancing understanding of their clinical and genetic profiles.
PubMed: 38919847
DOI: 10.22551/2024.43.1102.10286 -
Thorax Jun 2024
To progress or not to progress: new insights into the evolution of pleuropulmonary blastomas come from studying lung cysts in adolescents and adults with -related tumour predisposition.
Topics: Humans; Ribonuclease III; Pulmonary Blastoma; DEAD-box RNA Helicases; Adult; Adolescent; Genetic Predisposition to Disease; Lung Neoplasms; Cysts
PubMed: 38548329
DOI: 10.1136/thorax-2024-221459 -
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 -
Thorax Jun 2024Pleuropulmonary blastoma (PPB), the hallmark tumour associated with -related tumour predisposition, is characterised by an age-related progression from a cystic lesion...
Prevalence of lung cysts in adolescents and adults with a germline pathogenic/likely pathogenic variant: a report from the National Institutes of Health and International Pleuropulmonary Blastoma/ Registry.
BACKGROUND
Pleuropulmonary blastoma (PPB), the hallmark tumour associated with -related tumour predisposition, is characterised by an age-related progression from a cystic lesion (type I) to a high-grade sarcoma with mixed cystic and solid features (type II) or purely solid lesion (type III). Not all cystic PPBs progress; type Ir (regressed), hypothesised to represent regressed or non-progressed type I PPB, is an air-filled, cystic lesion lacking a primitive sarcomatous component. This study aims to evaluate the prevalence of non-progressed lung cysts detected by CT scan in adolescents and adults with germline pathogenic/likely pathogenic (P/LP) variants.
METHODS
Individuals were enrolled in the National Cancer Institute Natural History of Syndrome study, the International PPB/ Registry and/or the International Ovarian and Testicular Stromal Tumor Registry. Individuals with a germline P/LP variant with first chest CT at 12 years of age or older were selected for this analysis.
RESULTS
In the combined databases, 110 individuals with a germline P/LP variant who underwent first chest CT at or after the age of 12 were identified. Cystic lung lesions were identified in 38% (42/110) with a total of 72 cystic lesions detected. No demographic differences were noted between those with lung cysts and those without lung cysts. Five cysts were resected with four centrally reviewed as type Ir PPB.
CONCLUSION
Lung cysts are common in adolescents and adults with germline variation. Further study is needed to understand the mechanism of non-progression or regression of lung cysts in childhood to guide judicious intervention.
Topics: Adolescent; Adult; Child; Female; Humans; Male; Middle Aged; Young Adult; Cysts; DEAD-box RNA Helicases; Germ-Line Mutation; Lung Diseases; Lung Neoplasms; Prevalence; Pulmonary Blastoma; Registries; Ribonuclease III; Tomography, X-Ray Computed; United States; Aged
PubMed: 38508719
DOI: 10.1136/thorax-2023-221024 -
Journal of Bronchology & Interventional... Jan 2024
Topics: Humans; Pulmonary Blastoma; Kidney Neoplasms; Neoplastic Syndromes, Hereditary; Ribonuclease III; DEAD-box RNA Helicases
PubMed: 38014858
DOI: 10.1097/LBR.0000000000000955 -
Journal of Indian Association of... 2024
PubMed: 38912022
DOI: 10.4103/jiaps.jiaps_201_23 -
Gynecologic Oncology Reports Apr 2024Sertoli-Leydig cell tumors (SLCT) are a rare form of sex cord stromal tumors. germline mutations have been identified in a portion of these cases. We report a...
Sertoli-Leydig cell tumors (SLCT) are a rare form of sex cord stromal tumors. germline mutations have been identified in a portion of these cases. We report a 15-year-old individual who presented to a well-child visit with secondary amenorrhea and subjective observations of a deepening voice and broadening shoulders. Elevations were noted in serum testosterone, inhibin B, androstenedione, and DHEA. Pelvic ultrasound and magnetic resonance imaging (MRI) revealed a left ovarian complex lesion measuring 5.8 x 5.5 x 4.6 cm. A laparoscopic unilateral salpingo-oophorectomy was performed with negative pelvic washings and a diagnosis of stage 1A, poorly differentiated/grade 3 SLCT of the ovary. Somatic and germline testing both demonstrated pathologic variations. Adjuvant chemotherapy with cisplatin/etoposide/ifosfamide (PEI) was completed under the care of pediatric oncology, and this patient is now undergoing surveillance with no signs of recurrence. Syndrome is associated with multiple tumors, including SLCT, pleuropulmonary blastoma (PPB), cystic sarcomas, and Wilms tumor among others. Patients with SLCT found to have a mutation should undergo genetic testing and cancer screening, which may help to identify neoplasms associated with the mutation at an early stage. This case will serve as a useful addition to the literature and review suggested pre-operative, operative, and surveillance guidelines.
PubMed: 38571566
DOI: 10.1016/j.gore.2024.101353 -
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