scholarly journals Clinicopathological and Molecular Characteristics of Atypical Pulmonary Sclerosing Pneumocytoma With Multiple Metastases

2020 ◽  
Author(s):  
Qiushi Wang ◽  
Xiao Yang ◽  
Minrui Jiang ◽  
Mengxia Li ◽  
Lei Zhang ◽  
...  
Keyword(s):  
Copy Number ◽  
Copy Number Variations ◽  
Middle Lobe ◽  
High Copy Number ◽  
Pathological Examination ◽  
Control Group ◽  
Molecular Characteristics ◽  
Short Period ◽  
Multiple Metastases ◽  
The Right

Abstract Background: Few patients with pulmonary sclerosing pneumocytoma (PSP) may suffer from recurrence and oligometastasis as it is a benign tumor or has a low malignancy potential. Herein, an in-depth study, based on an extremely rare PSP case with atypical features, was carried out to elaborate the potential mechanism underlying the rapid malignant progression. Methods: The clinicopathological data of this atypical PSP (AP) case were obtained. Formalin‑fixed and paraffin‑embedded tissues from all the lesions of AP and five classic PSP cases (as control) were used for whole-exome sequencing (WES) and immunohistochemistry. Results: A 23-year-old male showed a 6.5-cm pulmonary nodule in the right middle lobe (RML) and enlarged mediastinal lymph nodes (LNs). He underwent thoracoscopic RML lobectomy, systematic LNs dissection, and mediastinal lymphadenectomy. The metastases to the cervical LNs and liver were detected in a short period and then resected. Postoperative pathological examination confirmed the diagnosis of PSP in all the lesions, based on the typical histological characteristics and immunophenotypes. Furthermore, WES identified both AKT1 E17K somatic mutation and TP53 C176Y germline mutation in this AP case. The genomic evolution analysis showed different evolutionary branches in the metastatic tumors distinct from the primary lesion. Moreover, compared to the control group, the AP case showed high copy number variations (CNVs) and significantly high copy number instability (CNI). Conclusions: We speculated that the atypical histopathological features and malignant behaviors may be due to the co-mutations of somatic AKT1 E17K and germline TP53 C176Y, combined with the high CNVs and CNI.

scholarly journals Carcinosarcoma of the prostate: case report with molecular and histological characterization

2018 ◽  
Vol 33 (4) ◽  
pp. 540-544 ◽  
Author(s):  
Samanta Salvi ◽  
Valentina Casadio ◽  
Filippo Martignano ◽  
Giorgia Gurioli ◽  
Maria Maddalena Tumedei ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Copy Number ◽  
Copy Number Variations ◽  
Molecular Characteristics ◽  
Glutathione S Transferase ◽  
Molecular Alterations ◽  
Positive Expression ◽  
Molecular Pattern ◽  
Programmed Death ◽  
Number Variation

Background: We report a case of prostatic carcinosarcoma, a rare variant of prostatic cancer, which is composed of a mixture of epithelial and mesenchymal components with a generally poor outcome. Aims and methods: We aim to identify molecular alterations, in particular copy number variations of AR and c -MYC genes, methylation and expression of glutathione S-transferase P1 (GSTP1), programmed death-ligand 1 (PD-L1), AR, and phosphorylated AR expression. Results: We found a distinct molecular pattern between adenocarcinoma and carcinosarcoma, which was characterized by high AR copy number variation gain; positive expression of PD-L1, AR, and phosphorylated AR; low espression of GSTP1 in epithelial component. The sarcomatoid component had a lower gain of the AR gene, and no expression of PD-L1, AR, phosphorylated AR, or GSTP1. Both components had a gain of c-MYC copy number variation. Conclusions: Our findings suggest that carcinosarcoma has specific molecular characteristics that could be indicative for early diagnosis and treatment selection.

scholarly journals Tomographic findings in bronchial atresia

2021 ◽  
Vol 54 (1) ◽  
pp. 9-14
Author(s):  
Elazir Barbosa Mota Di Puglia ◽  
Rosana Souza Rodrigues ◽  
Pedro Augusto Daltro ◽  
Arthur Soares Souza Jr. ◽  
Marilene Monteiro Paschoal ◽  
...  
Keyword(s):  
Lower Lobe ◽  
Lung Parenchyma ◽  
Pulmonary Involvement ◽  
Middle Lobe ◽  
Pathological Examination ◽  
Surgical Specimen ◽  
Distal Lung ◽  
The Right ◽  
Ct Finding ◽  
Bronchial Atresia

Abstract Objective: To evaluate computed tomography (CT) findings in 23 patients with bronchial atresia. Materials and Methods: The CT images were reviewed by two radiologists who reached decisions by consensus. We included only patients who presented with abnormalities on CT and in whom the diagnosis had been confirmed by pathological examination of the surgical specimen (if the lesion was resected). The CT scans were assessed in order to identify the main findings and to map the distribution of the lesions (i.e., to determine whether the pulmonary involvement was unilateral or bilateral). Results: The main CT finding was the combination of bronchocele and hyperinflation of the distal lung. That combination was observed in all of the patients. The lesions were unilateral in all 23 cases, being seen predominantly in the left upper lobe, followed by the right lower lobe, right upper lobe, middle lobe, and left lower lobe. Conclusion: The diagnosis of bronchial atresia can be reliably made on the basis of a finding of bronchocele accompanied by hyperinflation of the adjacent lung parenchyma.

scholarly journals Case Report and Literature Review: Pulmonary Sclerosing Pneumocytoma With Multiple Metastases Harboring AKT1 E17K Somatic Mutation and TP53 C176Y Germline Mutation

2021 ◽  
Vol 8 ◽  
Author(s):  
Qiushi Wang ◽  
Chunlin Lu ◽  
Minrui Jiang ◽  
Mengxia Li ◽  
Xiao Yang ◽  
...  
Keyword(s):  
Somatic Mutation ◽  
Germline Mutation ◽  
Molecular Genetic ◽  
Primary Lung Cancer ◽  
Middle Lobe ◽  
Biological Behavior ◽  
Pathological Examination ◽  
Regional Lymph Nodes ◽  
Genetic Changes ◽  
Short Period

Pulmonary Sclerosing Pneumocytoma (PSP) is considered as a benign tumor, although a few cases have been reported to have multiple lesions, recurrence, and even regional lymph nodes (LNs) metastasis. Here, we report a case of PSP with atypical histologic features and malignant biological behavior, and explore its molecular genetic changes. The 23-year-old male showed a 6.5-cm pulmonary nodule in the right middle lobe (RML) and enlarged media stinal LNs. He underwent thoracoscopic RML lobectomy, systematic LNs dissection, and mediastinal lymphadenectomy. The metastases to the cervical LNs and liver were detected in a short period and then resected. Postoperative pathological examination confirmed the diagnosis of PSP in all the lesions, based on the histological characteristics and immune phenotypes. Furthermore, whole-exome sequencing identified both AKT1 E17K somatic mutation and TP53 C176Y germline mutation in this case. Thus, we presented an extremely rare case of atypical PSP with rapid recurrence and multiply metastases, which can easily be misdiagnosed as primary lung cancer. In addition, PSP-specific AKT1 E17K somatic E17K somatic mutation accompanied with TP53 C176Y germline mutation may contribute to the malignant clinical course of this tumor.

scholarly journals Bilateral Choroidal Metastases as Presentation of Dissemination of Cutaneous Malignant Melanoma

2012 ◽  
Vol 2012 ◽  
pp. 1-3 ◽  
Author(s):  
S. Fernandez-Perez ◽  
O. Ruiz-Moreno ◽  
V. Pueyo ◽  
G. de la Mata ◽  
L. Pablo
Keyword(s):  
Malignant Melanoma ◽  
Cutaneous Melanoma ◽  
Posterior Pole ◽  
Cutaneous Malignant Melanoma ◽  
Pathological Examination ◽  
Blurred Vision ◽  
Pigmented Lesions ◽  
Multiple Metastases ◽  
Exhaustive Study ◽  
The Right

Case Report. A 47-year-old man presented with blurred vision in the right eye. Ophthalmoscopic examination showed several placoid, pigmented lesions in the posterior pole and midperiphery of the retina of both eyes.Results. Patient referred a cutaneous malignant melanoma on the back skin removed 6 years ago. A systemic workup revealed multiple metastases in liver and spleen. After an exhaustive study we concluded that it was a dissemination of a cutaneous malignant melanoma with bilateral choroidal metastases, liver and spleen metastases. The patient obtained clinical ocular improvement after palliative chemotherapy, although he died in the following months. Pathological examination of the lesions confirmed the diagnosis of choroidal metastases from a malignant cutaneous melanoma.Conclusions. Monitoring patients who have had cutaneous malignant melanoma is very important, since melanoma metastases may occur even many years after the diagnosis of the primary tumor. Choroidal metastases from cutaneous melanoma are uncommon but we should be aware because their appearance worsens prognosis.

scholarly journals Integrated Multiomics Analyses Revealing Different Molecular Profiles Between Early- and Late-Stage Lung Adenocarcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Dongsheng Yue ◽  
Weiran Liu ◽  
Liuwei Gao ◽  
Lianmin Zhang ◽  
Tao Wang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Cancer Progression ◽  
Late Stage ◽  
Copy Number ◽  
Copy Number Variations ◽  
Regulatory Mechanisms ◽  
Gene Copy ◽  
Molecular Characteristics ◽  
Open Chromatin ◽  
Copy Number Loss

The molecular differences in genetic and epigenetic profiling between early-stage (ES) and late-stage (LS) lung adenocarcinoma (LUAD), which might help to understand cancer progression and biomarker guided precision treatment, need further be investigated. In this study, we performed comprehensive analysis using multi-omics next-generation sequencing (NGS) on tissue samples from 7 ES (stage I) and 10 LS (stage III/IV) LUAD patients to study molecular characteristics between the two groups. Characterization of the genomic and transcriptomic profiles showed stage-specific somatic mutations, copy number variations (CNVs) and differentially expressed genes (DEGs). LS samples tend to have more TP53, ERBB2 and CHD4 mutations. Gene copy number loss occurs in immune-related gene pathways in the late stage of LUAD. ATAC-seq analysis showed that LS samples harbored more open chromatin peaks around promoter regions and transcription start sites (TSS) than ES samples. We then identified the known transcription factor (TF) binding motifs for the differentially abundant ATAC-seq peaks between the ES and LS samples and found distinct regulatory mechanisms related to each stage. Furthermore, integrative analysis of ATAC-seq with WGS and RNA-seq data showed that the degree of chromatin accessibility is related to copy number changes, and the open chromatin regions could directly regulate the expression of some DEGs. In conclusion, we performed a comprehensive multi-omics analysis of the early and late stages of LUAD and highlighted some important molecular differences in regulatory mechanisms during cancer progression. Those findings help to further understand mechanism and biomarker related targeted therapy.

scholarly journals Genomic Profiling Identified Novel Prognostic Biomarkers in Chinese Midline Glioma Patients

2021 ◽  
Vol 10 ◽  
Author(s):  
Hainan Li ◽  
Changguo Shan ◽  
Shengnan Wu ◽  
Baijie Cheng ◽  
Chongzu Fan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Overall Survival ◽  
Survival Data ◽  
Copy Number ◽  
Copy Number Variations ◽  
Prognostic Biomarkers ◽  
Occurrence Rate ◽  
Molecular Characteristics ◽  
Poor Overall Survival ◽  
Tissue Samples

BackgroundMolecular characteristics are essential for the classification and grading of gliomas. However, diagnostic classification of midline glioma is still debatable and substantial molecular and clinical heterogeneity within each subgroup suggested that they should be further stratified. Here, we studied the mutation landscape of Chinese midline glioma patients in hope to provide new insights for glioma prognosis and treatment.MethodsTissue samples from 112 midline glioma patients underwent next-generation sequencing targeting 425 cancer-relevant genes. Gene mutations and copy number variations were investigated for their somatic interactions and prognostic effect using overall survival data. Pathway-based survival analysis was performed for ten canonical oncogenic pathways.ResultsWe identified several currently established diagnostic and prognostic biomarkers of glioma, including TP53 (33%), EGFR (26%), TERT (24%), PTEN (21%), PIK3CA (14%), ATRX (14%), BRAF (13%), and IDH1/2 (6%). Among all genetic aberrations with more than 5% occurrence rate, six mutations and three copy number gains were greatly associated with poor overall survival (univariate, P < 0.1). Of these, TERT mutations (hazard ratio [HR], 3.00; 95% confidence interval [CI], 1.37–6.61; P = 0.01) and PIK3CA mutations (HR, 2.04; 95% CI, 1.08–3.84; P = 0.02) remained significant in multivariate analyses. Additionally, we have also identified a novel MCL1 amplification (found in 31% patients) as a potential independent biomarker for glioma (multivariate HR, 2.78; 95% CI, 1.53–5.08; P < 0.001), which was seldom reported in public databases. Pathway analyses revealed significantly worse prognosis with abnormal PI3K (HR, 1.81; 95% CI, 1.12–2.95; P = 0.01) and cell cycle pathways (HR, 1.97; 95% CI, 1.15–3.37; P = 0.01), both of which stayed meaningful after multivariate adjustment.ConclusionsIn this study, we discovered shorter survival in midline glioma patients with PIK3CA and TERT mutations and with abnormal PI3K and cell cycle pathways. We also revealed a novel prognostic marker, MCL1 amplification that collectively provided new insights and opportunities in understanding and treating midline gliomas.

Copy Number Variation of PROS1 and Protein S Deficiency Are Rare in a Population-Based Case-Control Study On Venous Thrombosis (MEGA study).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3166-3166
Author(s):  
Maria Carolina Pintao ◽  
Irene D Bezemer ◽  
Andrea Aparecida Garcia ◽  
Marieke C.H. de Visser ◽  
Carine J.M. Doggen ◽  
...  
Keyword(s):  
Risk Factor ◽  
Venous Thrombosis ◽  
Vitamin K ◽  
Copy Number ◽  
Genetic Basis ◽  
Conflicts Of Interest ◽  
Protein S ◽  
Population Based ◽  
Copy Number Variations ◽  
Control Group

Abstract Abstract 3166 Poster Board III-106 Protein S (PS) deficiency increases the risk of venous thrombosis (VT) in family studies, but it has been difficult to estimate the risk in population-based studies. Moreover, the genetic basis of PS deficiency is only poorly understood as in about 50% of PS deficient families no mutations are found by exon-targeted sequencing of the PS gene PROS1. Further, the laboratory diagnosis of PS deficiency is complicated by physiological variation due to age and sex, as well as interference by pregnancy, use of hormones and medication and vitamin K deficiency. We recently showed with the multiplex ligation-dependent probe amplification (MLPA) methodology, that whole or partial deletion of PROS1 explained PS deficiency in around 40% of point mutation-negative French PS deficient families. Here, we analyzed PS deficiency in the MEGA (Multiple Environmental and Genetic Assessment) study to verify whether gross gene deletions or duplications are also common in unselected individuals with venous thrombosis. The MEGA study included 5000 patients with a first episode of deep VT or pulmonary embolism and 5000 controls. Questionnaires and DNA samples were taken for every participant and blood was collected in around half of patients and controls. Total PS (tPS) was measured in plasma by ELISA. For analysis, vitamin K users were excluded yielding 2198 patients and 2904 controls. The mean tPS (±SD) was 102.6 U/dL (±19.1) in patients and 100.8 U/dL (±19.7) in controls. OR and 95% confidence interval were computed to estimate the relative risk of thrombosis. PS was not a risk factor for thrombosis in the MEGA study when deciles were used to calculate OR neither when lowest 2.5% or 1% PS levels was examined (data not shown). We then randomly analyzed DNA samples from 2270 participants out of 10000 individuals (1395 patients and 875 controls) by MLPA to look for copy number variations (CNVs). In only one individual an abnormal MLPA pattern was found and the test was repeated confirming results. This individual, a female patient of 66 years who was not using estrogens, was heterozygous for a deletion of the complete PROS1 gene. Her tPS was 64.3 U/dL, which was below the 2.5th percentile (tPS = 65.3 U/dL) of the total MEGA control group. To check if the frequency of CNVs in PROS1 was indeed low in the MEGA, we zoomed in on PS deficiency by selecting DNA from individuals with low tPS (cuttof: mean tPS -2SD of the total MEGA control group), not excluding vitamin K users. This selection yielded 404 individuals, out of which 198 had been previously analyzed in the first round. MLPA was performed for the remaining 206 individuals and no new CNV was found in PROS1. In conclusion, PS deficiency was not a risk factor for VT in this population-based study and deletions or duplications in PROS1 were not common. This is in contrast with previous data from family-based studies but in accordance with the fact that the genetic basis of PS deficiency and its risk for VT outside of a family setting was also not evident in other studies. Disclosures No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document