scholarly journals Establishment of Criteria for Molecular Differential Diagnosis of MPLC and IPM

2021 ◽  
Vol 10 ◽  
Author(s):  
Xiaohui Wang ◽  
Yuan Gong ◽  
Jianfei Yao ◽  
Yan Chen ◽  
Yuemin Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Differential Diagnosis ◽  
High Frequency ◽  
Validation Cohort ◽  
Primary Lung Cancer ◽  
Low Frequency ◽  
Gene Panel ◽  
Concordance Rate ◽  
Gene Alteration ◽  
Gene Alterations

BackgroundsDifferential diagnosis of multiple primary lung cancer (MPLC) and intrapulmonary metastasis (IPM) is one difficulty in lung cancer diagnosis, and crucial for establishment of treatment strategies and prognosis prediction. This study aims to establish the criteria for molecular differential diagnosis of synchronous MPLC and IPM by the next-generation sequencing (NGS) method.MethodsTraining cohort included 30 synchronous MPLC (67 samples) patients and 5 synchronous IPM (13 samples) patients with adenocarcinoma. Criteria of MPLC/IPM differential diagnosis were established by results from a NGS-based 605-gene panel test. Subsequently, 16 patients (36 samples) were recruited as the validation cohort to verify the criteria.ResultsIPM lesions showed a high degree of mutation overlap with an average concordance rate of 60.2% (range: 15.8%–91.7%). IPM lesions had at least three common alterations, including both high-frequency driver gene alterations and low-frequency gene alterations. In contrast, the average concordance rate of MPLC was 11.0% (range: 0.0%–100.0%), among which 66.7% (20/30) of patients had no common alterations (concordance rate: 0%). In the remaining 10 patients, 9 had only one overlapping alteration while 1 had two overlapping alterations, in which 6 patients had EGFR L858R overlapping mutation. Alterations were classified into trunk, shared, and branch subtypes. Branch alterations accounted for 94.4% of mutations in MPLC, while accounted for only 45.0% in IMP. In contrast, the ratio of trunk (38.3%) and shared (16.7%) alterations in IPM was significantly higher. The criteria for differentiating MPLC from IPM using 605-gene panel was established: 1) MPLC can be interpreted if no overlapping alterations is found; 2) MPLC is recommended if one overlapping high-frequency drive gene alteration and/or one overlapping low-frequency gene alteration are/is found; 3) IPM can be interpreted if more than three common alterations are found. Subsequently, 16 patients were recruited as the validation cohort in the single-blind manner to verify the criteria, and 14 MPLC and 2 IPM were identified, which was 100% consistent with the results from independent imaging and pathological diagnosis.ConclusionsNGS detection can distinguish synchronous MPLC from IPM and is a useful tool to assist differential diagnosis.

A Novel Adaptive PET/CT Image Fusion Algorithm

2019 ◽  
Vol 14 (7) ◽  
pp. 658-666
Author(s):  
Kai-jian Xia ◽  
Jian-qiang Wang ◽  
Jian Cai
Keyword(s):  
Lung Cancer ◽  
Image Fusion ◽  
High Frequency ◽  
Malignant Tumors ◽  
Low Frequency ◽  
Combination Method ◽  
Ct Image ◽  
Fusion Algorithm ◽  
Pet Ct ◽  
Frequency Components

Background: Lung cancer is one of the common malignant tumors. The successful diagnosis of lung cancer depends on the accuracy of the image obtained from medical imaging modalities. Objective: The fusion of CT and PET is combining the complimentary and redundant information both images and can increase the ease of perception. Since the existing fusion method sare not perfect enough, and the fusion effect remains to be improved, the paper proposes a novel method called adaptive PET/CT fusion for lung cancer in Piella framework. Methods: This algorithm firstly adopted the DTCWT to decompose the PET and CT images into different components, respectively. In accordance with the characteristics of low-frequency and high-frequency components and the features of PET and CT image, 5 membership functions are used as a combination method so as to determine the fusion weight for low-frequency components. In order to fuse different high-frequency components, we select the energy difference of decomposition coefficients as the match measure, and the local energy as the activity measure; in addition, the decision factor is also determined for the high-frequency components. Results: The proposed method is compared with some of the pixel-level spatial domain image fusion algorithms. The experimental results show that our proposed algorithm is feasible and effective. Conclusion: Our proposed algorithm can better retain and protrude the lesions edge information and the texture information of lesions in the image fusion.

scholarly journals Endotracheal Metastasis Causing Airway Obstruction

2020 ◽  
Vol 4 (1) ◽  
pp. 96-98
Author(s):  
Yudai Yano ◽  
Takashi Fujiwara ◽  
Masanobu Mizuta
Keyword(s):  
Computed Tomography ◽  
Lung Cancer ◽  
Emergency Department ◽  
Differential Diagnosis ◽  
Respiratory Symptoms ◽  
Primary Lung Cancer ◽  
Chest Computed Tomography ◽  
Important Differential Diagnosis ◽  
Emergency Tracheostomy ◽  
Rare Lesion

Endotracheal metastasis, a critical complication of primary lung cancer, is an extremely rare lesion. A 73-year-old woman who had previously received treatment for lung cancer presented to our emergency department with dyspnea. A chest computed tomography and nasopharyngolaryngoscopy showed an endotracheal mass below the epiglottis, obstructing the trachea almost completely. The patient had an emergency tracheostomy, and then the mass was removed via median laryngotomy. This lesion was proven to be a recurrent metastasis of lung cancer. Clinicians should recognize endotracheal metastasis as an important differential diagnosis in cancer patients presenting with respiratory symptoms.

The molecular and immune characteristics, antitumor activity of crizotinib in non-small cell lung cancer (NSCLC) patients with MET exon 14 skipping alterations.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20588-e20588
Author(s):  
Jiadi Gan ◽  
Wenfeng Fang ◽  
Weineng Feng ◽  
Jiexia Zhang ◽  
Huojin Deng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Antitumor Activity ◽  
High Frequency ◽  
Low Frequency ◽  
Small Cell ◽  
Splice Sites ◽  
Small Cell Lung ◽  
Tumor Region ◽  
Nsclc Patients

e20588 Background: MET exon 14 ( METex14) skipping caused by certain mutations in splice sites of METex14 has been regarded as a promising target for non-small cell lung cancer (NSCLC) treatment with crizotinib, and was observed with lower responsiveness to immunotherapy (Joshua K. et al ASCO 2017). The molecular and immune characteristics, antitumor activity of crizotinib for Chinese NSCLC patients harboring METex14 skipping alterations remain to be elucidated. Methods: Tumor genomic profiling was performed by next-generation sequencing (NGS) assay (GeneCast Biotechnology Co., Beijing) on 9722 samples (FFPE and/or peripheral blood derived from 9289 Chinese NSCLC patients). PD-L1 expression was determined by qualitative immunohistochemical assay. Multiplex immunohistochemistry (mIHC) analysis was adopted to evaluate the immune microenvironment of selected samples. Retrospective analysis was performed to explore antitumor activity of crizotinib monotherapy in 10 patients harboring METex14 skipping alterations. Results: A total of 62 (0.67%) patients with somatic mutations occurred in METex14 splice sites (± 3bp) were identified. Median age of these patients is 64.5 years and 39% patients are female. Main histologic types are adenocarcinoma (81%, 50/62) and squamous carcinoma (13%, 8/62). 30 patients harbored high frequency METex14 mutations ranged from 1.34% to 79.49% nearly without co-existed known driver variants. Other 32 patients had low frequency mutations (below 1%) with some crucial oncogenic mutations such as EGFR 19del/L858R. In addition, very few CD8+ T cells were observed in tumor region and significantly less infiltrated than in stroma region ( P< 0.01). The overall response rate of crizotinib monotherapy on the ten patients with METex14 skipping alterations was 70% (7/10 achieved partial response), with progression free survival range from 3 to 20 months. Conclusions: The occurrence rate of METex14 skipping mutations in Chinese NSCLC patients is low. Low frequency ( < 1%) METex14 mutations usually co-exist with other driver mutations while high frequency METex14 mutations do not. That little infiltration of CD8+ T cells in tumor region might be associated with poor responsiveness of NSCLC patients carrying METex14 skipping alterations to immunotherapy. Our clinical cases exhibited promising antitumor activity of crizotinib in Chinese NSCLC patients harboring METex14 skipping alterations.

scholarly journals Next-generation sequencing facilitates differentiating between multiple primary lung cancer and intrapulmonary metastasis: a case series

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Changjiang Liu ◽  
Chengang Liu ◽  
Xiao Zou ◽  
Lin Shao ◽  
Ying Sun ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Differential Diagnosis ◽  
Primary Lung Cancer ◽  
Invasive Adenocarcinoma ◽  
Free Survival ◽  
Multiple Primary ◽  
Minimally Invasive Adenocarcinoma ◽  
The Right ◽  
Generation Sequencing

Abstract Background In lung cancer management, differential diagnosis between multiple primary lung cancer (MPLC) and intrapulmonary metastasis (IMP) is a critical point that is of direct therapeutic and clinical importance. However, this process often suffers from absence of a gold standard, resulting in equivocal cases. Herein, we present a series of three cases, in which genomic alteration patterns revealed by next-generation sequencing (NGS) facilitated the differential diagnosis between MPLC and IMP. Case presentation Case 1 was a 57-year-old female with two separate lesions in the upper lobe and the lower lobe of left lung, which were both histopathologically determined as T2aN0M0 adenocarcinomas. NGS identified an EGFR L858R in one lesion and an EGFR 20 exon insertion in the other one, suggestive of double primary malignancies. The patient underwent wedge resections and received an adjuvant treatment of icotinib and chemotherapy. She had a disease-free survival (DFS) of 19 months and counting. Case 2 was a 55-year-old female with multiple small lesions in both lungs. Histopathological examinations of resected lesions from right upper lobe revealed three subtypes: atypical adenomatous hyperplasia of alveolar epithelium, adenocarcinomas in situ and minimally invasive adenocarcinoma. NGS identified two different BRAF driver mutations G466E and V600_K601delinsE in two lesions of adenocarcinoma in situ, and a BRAF K601E in a lesion of minimally invasive adenocarcinoma. Case 3, a 68-year-old male, had the right upper lobe lesion histophathologically classified as a stage T3NxM0 mixed adenoneuroendocrine carcinoma and the left upper lobe lesion as a stage T1aN0M0 adenocarcinoma. NGS performed with different loci of surgical tissues revealed a rare sensitizing EGFR mutation G719A shared by the right upper lobe lesion and lymph node, and two EGFR mutations L861Q and G719S in left upper lobe lesion. The patient received icotinib treatment postoperatively and achieved a stable disease with a progression-free survival of 5 months. Conclusion Our cases provide evidence for utility of NGS in facilitating diagnosis and treatment decisions.

scholarly journals CLCA2 as a Novel Immunohistochemical Marker for Differential Diagnosis of Squamous Cell Carcinoma from Adenocarcinoma of the Lung

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Kazuya Shinmura ◽  
Hisaki Igarashi ◽  
Hisami Kato ◽  
Yuichi Kawanishi ◽  
Yusuke Inoue ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Differential Diagnosis ◽  
Protein Expression ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Primary Lung Cancer ◽  
The Cancer Genome Atlas ◽  
Immunohistochemical Marker ◽  
Expression Status

Recent progress in targeted therapy for lung cancer has revealed that accurate differential diagnosis between squamous cell carcinoma (SCC) and adenocarcinoma (ADC) of the lung is essential. To identify a novel immunohistochemical marker useful for differential diagnosis between the two subtypes of lung cancer, we first selected 24 SCC-specific genes and 6 ADC-specific genes using data (case number, 980) from the Cancer Genome Atlas (TCGA) database. Among the genes, we chose theCLCA2gene, which is involved in chloride conductance and whose protein expression in lung cancer is yet to be characterized, and evaluated its protein expression status in 396 cases of primary lung cancer at Hamamatsu University Hospital. Immunohistochemical analysis revealed a significantly higher CLCA2 expression level in the SCCs than in the ADCs(P<0.0001)and also a significantly higher frequency of CLCA2 protein expression in the SCCs (104/161, 64.6%) as compared with that in the ADCs (2/235, 0.9%)(P<0.0001; sensitivity 64.6%, specificity 99.1%). The CLCA2 protein expression status was associated with the histological tumor grade in the SCCs. These results suggest that CLCA2 might be a novel excellent immunohistochemical marker for differentiating between primary SCC and primary ADC of the lung.

scholarly journals Significance of Earlier Initiation of Chemotherapy for Lung Cancer Complicated with Primary or Secondary Nephrotic Syndrome following Its Appropriate Differential Diagnosis

2019 ◽  
Vol 12 (1) ◽  
pp. 53-58 ◽  
Author(s):  
Shuji Ota ◽  
Yoshihide Fujigaki ◽  
Yoshifuru Tamura ◽  
Kenichiro Kojima ◽  
Ryosuke Ochiai ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Differential Diagnosis ◽  
Nephrotic Syndrome ◽  
Membranous Nephropathy ◽  
Performance Status ◽  
Primary Lung Cancer ◽  
Definitive Diagnosis ◽  
Primary Nephrotic Syndrome ◽  
Significant Toxicity ◽  
Secondary Nephrotic Syndrome

We encountered a case of primary lung cancer complicated with membranous nephropathy as primary nephrotic syndrome. Because treatment approaches vary greatly for primary and secondary nephrotic syndrome, a renal biopsy was performed for diagnosis. Much time was required to make a definitive diagnosis of primary nephrotic syndrome, as opposed to paraneoplastic nephrotic syndrome. Consequently, the subsequent chemotherapy was ineffective and caused significant toxicity due to reduced performance status (PS) and progression of hypoalbuminemia. Therefore, it is imperative that a diagnosis be made and treatment be initiated without delay before PS declines and hypoalbuminemia progresses.

scholarly journals Plasma Metabolomics Study in Lung Cancer Screening and Differential Diagnosis

2021 ◽  
Author(s):  
Zixu Liu ◽  
Lei Guo ◽  
Shuai Liu ◽  
Minjun Du ◽  
Yicheng Liang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Differential Diagnosis ◽  
Pulmonary Nodule ◽  
Primary Lung Cancer ◽  
Pulmonary Nodules ◽  
Lung Cancer Screening ◽  
Population Group ◽  
Healthy People ◽  
Healthy Population ◽  
Validation Set

Abstract [Objectives] By studying the plasma metabolomics of patients with different pulmonary nodules and healthy people, we can find the difference in plasma low-molecular metabolites among them. [Methods] Patients with pulmonary nodules admitted to our department were divided into three groups: pulmonary metastatic carcinoma (PMC), benign pulmonary nodules (BPN), and primary lung cancer (PLC). Meanwhile healthy people were enrolled as healthy population group (HPG). PLC and HPG were equally divided into the Discovery Set and Validation set. [Results] Five significant low-molecular metabolites were found by comparison of four groups as a whole. Four to six metabolites were selected by comparison of the three pulmonary nodule groups with healthy people respectively. The AUC of ROC of these metabolites were all＞0.93. Each pairwise comparison within the three pulmonary nodule groups all found three metabolites, whose AUC of ROC were all＞0.83. From the comparison of PLC and HPG in the discovery set, six metabolites were selected. Their AUC of ROC were all greater than 0.95 in the validation set, indicating that they had a strong ability to differentiate between primary lung cancer and healthy people. [Conclusions] We can find the significant changes of some low-molecular metabolites among three pulmonary nodules and healthy people. These metabolites had the potential to be biomarkers for screening and differential diagnosis of lung cancer.

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