scholarly journals Undifferentiated large cell/rhabdoid carcinoma presenting in the intestines of patients with concurrent or recent non-small cell lung cancer (NSCLC): clinicopathologic and molecular analysis of 14 cases indicates an unusual pattern of dedifferentiated metastases

2021 ◽  
Author(s):  
Abbas Agaimy ◽  
Ondrej Daum ◽  
Michal Michal ◽  
Mona W. Schmidt ◽  
Robert Stoehr ◽  
...  

AbstractUndifferentiated carcinoma metastatic to the bowel is uncommon in surgical pathology practice and might be confused with primary gastrointestinal carcinoma, melanoma, lymphoma, and others. We present 14 cases of uni- (n = 9) or multifocal (n = 5) undifferentiated large cell/rhabdoid carcinoma presenting in the bowel of patients with concurrent (n = 9) or recent (diagnosed 1 to 25 months earlier; median, 4) non-small cell lung cancer (NSCLC). Patients were 6 females and 8 males, aged 52 to 85 years. Primary NSCLC was verified histologically in 10 cases and by imaging in 4. The undifferentiated histology was present in the lung biopsy in 4/10 patients (as sole pattern in 3 and combined with adenocarcinoma in 1) and was limited to the intestinal metastases in the remainder. PDL1 was strongly expressed in 7/9 cases (CPS: 41 to 100). Loss of at least one SWI/SNF subunit was detected in 7/13 cases (54%). SMARCA2 loss (n = 6) was most frequent and was combined with SMARCA4 loss in one case. PBRM1 loss was observed in one tumor. Successful molecular testing of 11 cases revealed BRAF mutations in 4 (3 were non-V600E variants), KRAS mutations in 3, and wildtype in 4. None had EGFR mutations. Analysis of 4 paired samples revealed concordant KRAS (2) and BRAF (1) mutations or wildtype (1). Our study indicates that undifferentiated carcinoma within the intestines of patients with concurrent/recent NSCLC represents dedifferentiated metastasis from the NSCLC. Recognition of this unusual presentation is cardinal to avoid misdiagnosis with inappropriate therapeutic and prognostic implications.

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2084
Author(s):  
Roberto Martin-Deleon ◽  
Cristina Teixido ◽  
Carmen Mª Lucena ◽  
Daniel Martinez ◽  
Ainhoa Fontana ◽  
...  

Clinical guidelines promote the identification of several targetable biomarkers to drive treatment decisions in advanced non-small cell lung cancer (NSCLC), but half of all patients do not have a viable biopsy. Specimens from endobronchial-ultrasound transbronchial needle aspiration (EBUS-TBNA) are an alternative source of material for the initial diagnosis of NSCLC, however their usefulness for a complete molecular characterization remains controversial. EBUS-TBNA samples were prospectively tested for several biomarkers by next-generation sequencing (NGS), nCounter, and immunohistochemistry (PD-L1). The primary objectives were to assess the sensitivity of EBUS-TBNA samples for a comprehensive molecular characterization and to compare its performance to the reference standard of biopsy samples. Seventy-two EBUS-TBNA procedures were performed, and 42 NSCLC patients were diagnosed. Among all cytological samples, 92.9% were successfully genotyped by NGS, 95.2% by nCounter, and 100% by immunohistochemistry. There were 29 paired biopsy samples; 79.3% samples had enough tumor material for genomic genotyping, and 96.6% for PD-L1 immunohistochemistry. A good concordance was found between both sources of material: 88.9% for PD-L1, 100% for NGS and nCounter. EBUS-TBNA is a feasible alternative source of material for NSCLC genotyping and allows the identification of patient candidates for personalized therapies with high concordance when compared with biopsy.


2017 ◽  
Vol 70 (9) ◽  
pp. 803-806 ◽  
Author(s):  
Roberta Sgariglia ◽  
Pasquale Pisapia ◽  
Mariantonia Nacchio ◽  
Caterina De Luca ◽  
Francesco Pepe ◽  
...  

In the advanced stages of non-small cell lung cancer (NSCLC), molecular testing is often performed on archival cytological smears. The nCounter system (NanoString Technologies) is a new promising multiplex digital colour-coded barcode technology. However, its feasibility to evaluate the RNA expression of clinical relevant biomarkers on routine cytological smears is still uncertain. To this end, RNA was extracted from 12 NSCLC routine stained cytological smears, and nCounter analysis performed by using a 48-gene panel. Overall, 11/12 (92%) of the smears were adequate for the secondary analysis, fulfilling the quality check parameter analysis of nSolver software. This pilot study shows that RNA nCounter analysis is feasible on routine cytological smears preparing the field for the implementation of this technology in the routine setting.


2016 ◽  
Vol 23 (3) ◽  
pp. 280 ◽  
Author(s):  
K. Zibrik ◽  
J. Laskin ◽  
C. Ho

Nurse navigation is a developing facet of oncology care. The concept of patient navigation was originally created in 1990 at the Harlem Hospital Center in New York City as a strategy to assist vulnerable and socially disadvantaged populations with timely access to breast cancer care. Since the mid-1990s, navigation programs have expanded to include many patient populations that require specialized management and prompt access to diagnostic and clinical resources. Advanced non-small-cell lung cancer is ideally suited for navigation to facilitate efficient assessment in this fragile patient population and to ensure timely results of molecular tests for first-line therapy with appropriately targeted agents. At the BC Cancer Agency, nurse navigator involvement with thoracic oncology triage has been demonstrated to increase the proportion of patients receiving systemic treatment, to shorten the time to delivery of systemic treatment, and to increase the rate of molecular testing and the number of patients with molecular testing results available at time of initial consultation. Insights gained through the start-up process are briefly discussed, and a framework for implementation at other institutions is outlined.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7136-7136 ◽  
Author(s):  
G. Wagenius ◽  
O. Brodin ◽  
J. Nyman ◽  
G. Greim ◽  
G. Hillerdal ◽  
...  

7136 Background: Metastasis to the brain is the most common intracranial tumour and 20–40% of all cancer patients will develop brain metastases. Lung cancer is the most common primary tumour and compose of 40%-50% of all brain metasases. As the survival in many malignancies increases, brain metastases will be an increasing problem. It is therefore important to find new treatment options. The aim of this study was primary to study quality of life and to compare radiotherapy and Themozolomide in that context. Methods: Inclusion criterias were confirmed small cell or non-small cell lung cancer, multiple brain metastases, PS 0–2, no previous radiotherapy to the brain. Previous chemotherapy was allowed. Patients were randomized to arm A (radiotherapy 30 Gy over 10 fractions) or arm B (Temozolomide 200 mg/m2 day 1–5, new cycle on day 29). Quality of life (QoL) was measured with a general cancer module, EORTC QLQ-C30, and a brain cancer specific module, BCM20. The primary end-point was the proportion of patients in each treatment arm with maintained or better QoL score at 8 weeks compared to the base line evaluation. In this first analysis exclusion rate from the study at 8 weeks was used as a surrogate end-point. Results: 208 patients were included, 104 in arm A and 104 in arm B. 36 (17%) squamous cell, 97 (47%) adenocarcinomas, 10 (5%) large cell, 23 (11%) undifferentiated and 42 (20%) small-cell lung cancer were included. 93 (45%) patients were chemonaive. At 8 weeks, 79 patients were excluded from the study, 51 (49%) from the temozolomide arm and 28 (27%) from the radiotherapy arm. 53% of the patients with squamous cell carcinoma were excluded compared to 40% of small cell lung cancer, 33% of adenocarcinomas and 27% of large cell carcinomas. The exclusion rate at 8 weeks was higher among patients with symptoms at randomization compared to patients without symptoms. There were no difference in exclusion rate when comparing number or size of the metastases. Conclusion: The exclusion rate at 8 weeks was higher in the temozolomide arm compared to the radiotherapy arm. Histopathology and symptoms at randomization seems to be factors influencing the exclusion rate whereas number or size of metastases does not. Survival and quality of life data will be presented at the meeting. No significant financial relationships to disclose.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13018-e13018
Author(s):  
Jun Li ◽  
Cuiyun Zhang ◽  
Jiuzhou Zhao ◽  
Zhizhong Wang ◽  
Bing Wei ◽  
...  

e13018 Background: In recent years, the prognosis of non-small cell lung cancer (NSCLC) patients has been substantially improved by targeted therapies against specific molecular aberrations, i.e. tyrosine kinase inhibitors (TKIs) for Epidermal Growth Factor Receptor ( EGFR) etc. Several genes have been suggested by NCCN guideline (v7.2017) to test for NSCLC patients, including EGFR, ALK, ROS1, BRAF, MET, RET, HER2 and KRAS. The aim of this study is to profile the landscape of actionable mutations in Chinese NSCLC patients. Methods: From 2015 to 2017 621 treatment naïve NSCLC patients enrolled in the affiliated cancer hospital of Zhengzhou University were included in this analysis. DNA was extracted from the FFPE biopsies of these patients and processed for target capture sequencing covering the exons and flanking splicing regions of the 8 genes suggested by NCCN guideline, as well as introns of ROS, ALK and RET. Results: In total, 593 out of the 621 NSCLC patients harbor one or more mutations in these 8 genes, accounting for 95.5% of all the cases. EGFR, ALK and HER2 are the top 3 mutants, with a frequency of 52%, 32% and 26% respectively. Genetic aberrations in BRAF, MET, ROS1, KRAS and RET occur in 22%, 18%, 16% and 14% of the patients. The most common variation is missense; T > G, C > T and C > A changes are more often observed than T > C, T > A and C > G; the median number of variants per sample is 2, ranging from 1 to 13. There are 418 mutations detected on EGFR, of which 206 (49.28%) are clinically relevant. EGFR L858R, Exon19 deletion, Exon20 insertion, G719, A750P were observed in 123 (29.43%), 43 (10.29%), 8 (1.91%), 6 (1.44%) and 6 (1.44%) cases respectively. Gene fusions were identified in 78 cases, and the EML4- ALK is the most common one occurred in 54 patients, other fusion genes include KIF5B- ALK (11) , CCDC6- RET (4), CD74- ROS1 (4), EZR- ROS1 (2), ERC1- RET (1), , SDC4- ROS1 (1) and TCOF1- ROS1 (1). Conclusions: Target sequencing of the 8 genes suggested by NCCN guideline for NSCLC patients reveals essential information for designing personalized therapeutic regimen. Chinese patients, maybe other Asian countries also, may benefit more from this molecular testing, because of the high occurrence of actionable mutations.


The Lancet ◽  
2016 ◽  
Vol 388 (10048) ◽  
pp. 1002-1011 ◽  
Author(s):  
Crispin T Hiley ◽  
John Le Quesne ◽  
George Santis ◽  
Rowena Sharpe ◽  
David Gonzalez de Castro ◽  
...  

Molecular testing and the development of targeted therapies have revolutionized the treatment of non-small cell lung cancer (NSCLC). Despite the advantages of molecular testing in patients with NSCLC and guideline recommendations, there is no specific standard testing method, resulting in variable testing practices based on institution protocol and access. Pharmacists can help to improve coordination of care around appropriate testing as results are important in determining the most appropriate targeted treatment course. The majority of patients with NSCLC are tested for PD-L1, EGFR, ALK, ROS1, and BRAF mutations. These biomarkers and their corresponding targeted therapies are more understood than the remaining biomarkers, such as KRAS, RET, MET exon 14 (METex14), and NTRK. Multiple new and emerging therapies target these latter biomarkers, and this article will focus on these lesser-known biomarkers. As the treatment of NSCLC becomes increasingly biomarker-driven and more therapies are added to the armamentarium for the management of NSCLC, pharmacists will be called upon to assist the oncology care team to optimize NSCLC treatment to improve patient outcomes.


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