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- There has been a paradigm shift in the understanding of molecular pathogenesis of lung cancer. A number of oncogenic drivers have been identified in non-small cell lung carcinoma, such as the epidermal growth factor receptor ( EGFR) mutation and anaplastic lymphoma kinase ( ALK) gene rearrangement. Because of the clinical presentation at an advanced stage of disease in non-small cell lung carcinoma patients, the use of minimally invasive techniques is preferred to obtain a tumor sample for diagnosis. These techniques include image-guided biopsies and fine-needle aspirations, and frequently the cytology specimen may be the only tissue sample available for the diagnosis and molecular testing for these patients. - To review the current literature and evaluate the role of cytology specimens in lung cancer mutation testing. We reviewed the types of specimens received in the laboratory, specimen processing, the effect of preanalytic factors on downstream molecular studies, and the commonly used molecular techniques for biomarker testing in lung cancer. - PubMed and Google search engines were used to review the published literature on the topic. - Mutation testing is feasible on a variety of cytologic specimen types and preparations. However, a thorough understanding of the cytology workflow for the processing of samples and appropriate background knowledge of the molecular tests are necessary for triaging, and optimum use of these specimens is necessary to guide patient management.

Somatic mutations in (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4) gene and/or BRG1 (Brahma-related gene 1) loss identifies a subset of non-small cell lung carcinomas (NSCLCs) lacking alterations in (epidermal growth factor receptor), (anaplastic lymphoma kinase), and (ROS proto-oncogene 1) genes. Preliminary observations suggest responsiveness to immunotherapy and targeted therapies. To study BRG1 loss in NSCLCs and elucidate the clinicopathologic profile of such SMARCA4-deficient NSCLCs. Non-small cell lung carcinomas diagnosed during 6 years were subject to immunohistochemistry for BRG1 and BRM (Brahma). Tumors with BRG1 loss were stained with antibodies against thyroid transcription factor 1 (TTF-1), p40, cytokeratins, hepatocyte paraffin 1 (Hep Par 1), Sal-like protein 4 (SALL4), CD34, SRY-box 2 (SOX2), chromogranin, synaptophysin, p53, integrase interactor 1, ALK, and ROS1. mutation testing was performed by polymerase chain reaction-based method. Among 100 NSCLCs tested, 4 cases (4%) showed BRG1 loss. The histology ranged from solid adenocarcinomas (n = 1) to large cell/poorly differentiated carcinomas (n = 3) with clear cell cytology in 2 cases. All showed loss/reduction of BRM with variable cytokeratin and SALL4 expression, and were negative for TTF-1, p40, Hep Par 1, ALK, ROS1, and mutations. CD34 and SOX2 were negative in all 4 cases. Isolated BRM loss was common (21%), distributed across all NSCLC subtypes including squamous cell carcinomas and a hepatoid adenocarcinoma. BRG1 loss occurs in a subset of TTF-1/p40-negative poorly differentiated NSCLCs. Identification and follow-up will clarify the prognosis, diagnostic criteria, and potential for therapeutic personalization.

Angiotensin-converting enzyme 2 (ACE2) is a key host protein by which severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) enters and multiplies within cells. The level of ACE2 expression in the lung is hypothesised to correlate with an increased risk of severe infection and complications in COrona VIrus Disease 2019 (COVID-19). To test this hypothesis, we compared the protein expression status of ACE2 by immunohistochemistry (IHC) in post-mortem lung samples of patients who died of severe COVID-19 and lung samples obtained from non-COVID-19 patients for other indications. IHC for CD61 and CD163 was performed for the assessment of platelet-rich microthrombi and macrophages, respectively. IHC for SARS-CoV-2 viral antigen was also performed. In a total of 55, 44 COVID-19 post-mortem lung samples were tested for ACE2, 36 for CD163, and 26 for CD61, compared to 15 non-covid 19 control lung sections. Quantification of immunostaining, random sampling, and correlation analysis were used to substantiate the morphologic findings. Our results show that ACE2 protein expression was significantly higher in COVID-19 post-mortem lung tissues than in controls, regardless of sample size. Histomorphology in COVID-19 lungs showed diffuse alveolar damage (DAD), acute bronchopneumonia, and acute lung injury with SARS-CoV-2 viral protein detected in a subset of cases. ACE2 expression levels were positively correlated with increased expression levels of CD61 and CD163. In conclusion, our results show significantly higher ACE2 protein expression in severe COVID-19 disease, correlating with increased macrophage infiltration and microthrombi, suggesting a pathobiological role in disease severity.

Lung cancer (LC) is the leading cause of cancer-related mortality. Unfortunately, most patients of LC present at the advanced stage of the disease with a poor prognosis and 1-year survival of less than 20%. At the advanced stage of the disease, surgical resection cannot be possible, hence small biopsy or cytology specimens remain a choice for their correct diagnosis. The recognition of molecular drivers has revolutionized the treatment paradigm of non-small cell lung cancer (NSCLC) with introduction of tyrosine kinase inhibitors. Epidermal growth factor receptor (EGFR) gene mutations were identified, first, to be targeted in NSCLC followed by activating fusions in anaplastic lymphoma kinase (ALK) and rearrangements in c-ros oncogene 1 (ROS1) genes. In addition, the encouraging progress of immunotherapy in patients with NSCLC has been associated with predictive biomarker testing in the form of programmed death ligand-1 (PD-L1) immunohistochemistry assay. To test for these alterations, accurate biomarker testing is needed from biopsy or cytology specimens. In this brief review, testing of biomarkers is discussed using cytology specimens.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has recently emerged as a minimally invasive and safe modality for the evaluation of mediastinal lymphadenopathy, particularly in staging of lung carcinoma patients. In high tuberculosis endemic countries, EBUS-TBNA is useful in obtaining tissue diagnosis of granulomatous inflammation. Role of EBUS-TBNA in workup of extrapulmonary malignancies is not widely described. Herein, a brief overview of importance of EBUS-TBNA in investigation of extrapulmonary lesions/malignancies is presented.

Primary lung epithelial malignancies are the most common neoplasms among all pulmonary tumors. Lung cancer (LC) is the leading cause of cancer-related mortality for which a histologic or cytologic confirmation of malignancy is required before treatment. Specimen management is an important task for pathologists in the field of LC. Biopsy and fine needle aspiration are comparable. It is desirable to have both for diagnosis and mutation testing to maximize their use for patient care.

- Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has emerged as a very useful tool in the field of diagnostic respiratory cytology. Rapid on-site evaluation (ROSE) of EBUS-TBNA not only has the potential to improve diagnostic yield of the procedure but also to triage samples for predictive molecular testing to guide personalized treatments for lung cancer. - To provide an overview of the current status of the literature regarding ROSE of EBUS-TBNA in the diagnosis of lung cancer. - An electronic literature search in PubMed and Google databases was performed using the following key words: cytology, lung cancer, on-site evaluation, rapid on-site evaluation, and ROSE EBUS-TBNA. Only articles published in English were included in this review. - Rapid on-site evaluation can ensure that the targeted lesion is being sampled and can enable appropriate specimen triage. If available, it should be used with EBUS-TBNA in the diagnosis of lung cancer because it can minimize repeat procedures for additional desired testing (ie, molecular studies). Some studies have shown that ROSE does not adversely affect the number of aspirations, total procedure time of EBUS-TBNA, or the rate of postprocedure complications; it is also helpful in providing a preliminary diagnosis that can reduce the number of additional invasive procedures, such as mediastinoscopy. As EBUS technology continues to evolve, our knowledge of the role of ROSE in EBUS-TBNA for the diagnosis of lung cancer will also continue to grow and evolve.

Transition metal complexes of Co(II), Ni(II) and Cu(II) metal ions with general stoichiometry [M(L)X]X and [M(L)SO4], where M = Co(II), Ni(II) and Cu(II), L = 3,3’-thiodipropionic acid bis(4-amino-5-ethylimino-2,3-dimethyl-1-phenyl-3-pyrazoline) and X = NO3-, Cl- and OAc-, have been synthesized and structurally characterized by elemental analyses, molar conductance measurements, magnetic susceptibility measurements and spectral techniques like IR, UV and EPR. The nickel(II) complexes were found to have octahedral geometry, whereas cobalt(II) and copper(II) complexes were of tetragonal geometry. The covalency factor (β) and orbital reduction factor (k) suggest the covalent nature of the complexes. The ligand and its complexes have been screened for their antifungal and antibacterial activities against three fungi, i.e. Alternaria brassicae, Aspergillus niger and Fusarium oxysporum and two bacteria, i.e. Xanthomonas compestris and Pseudomonas aeruginosa.

The assessment of capsular invasion is an essential but challenging step in the diagnosis of encapsulated follicular thyroid neoplasms. Therefore, interobserver agreement in the assessment of capsular invasion in these tumors was investigated among 11 thyroid pathologists by using virtual slides of 20 cases in which the original diagnosis considered the differential diagnosis of definite capsular invasion versus questionable capsular invasion. The assessment of capsular invasion was divided into three categories: (1) non-invasive, (2) questionable invasive, and (3) clear-cut invasive. The interobserver agreements for clear-cut invasive and non-invasive categories were fair (Kappa value = 0.578 and 0.404, respectively), whereas agreement for the questionable invasion was poor (Kappa value = 0.186). Disagreements in the assessment of invasion resulted in variable final pathological diagnoses. For example, the agreement for a diagnosis of malignancy was only fair (Kappa value = 0.545). Moreover, pathologists did not have a uniform approach for rendering a final diagnosis in cases with questionable capsular invasion, though nine of 11 pathologists did use the follicular tumor of uncertain malignant potential diagnosis as proposed by the World Health Organization classification of endocrine organs published in 2017. In conclusion, this study revealed considerable interobserver variation in the evaluation of capsular invasion, especially in follicular neoplasms with questionable invasion.

The hippo pathway and its downstream mediator yes-associated protein 1 (YAP1) regulate mammalian organ size in part through modulating progenitor cell numbers. YAP1 has also been implicated as an oncogene in multiple human cancers. Currently, little is known about the expression of YAP1 either in normal human brain tissue or in central nervous system neoplasms. We used immunohistochemistry to evaluate nuclear YAP1 expression in the fetal and normal adult human brains and in 264 brain tumors. YAP1 was expressed infetal and adult brain regions known to harbor neural progenitor cells, but there was little YAP1 immunoreactivity in the adult cerebral cortex. YAP1 protein was also readily detected in the nuclei ofhuman brain tumors. In medulloblastoma, the expression varied between histologic subtypes and was most prominent in nodular/desmoplastic tumors. In gliomas, it was frequently expressed in infiltrating astrocytomas and oligodendrogliomas but rarely in pilocytic astrocytomas. Using a loss-of-function approach, we show thatYAP1 promoted growth of glioblastoma cell lines in vitro. High levels of YAP1 messenger RNA expression were associated with aggressive molecular subsets of glioblastoma and with a nonsignificanttrend toward reduced mean survival in human astrocytoma patients. These findings suggest that YAP1 may play an important rolein normal human brain development and that it could represent a new target in human brain tumors.