Resistance to osimertinib in advanced EGFR-mutated NSCLC: a prospective study of molecular genotyping on tissue and liquid biopsies.

Background: Resistance to osimertinib in advanced EGFR-mutated non-small cell lung cancer (NSCLC) constitutes a significant challenge for clinicians either in terms of molecular diagnosis and subsequent therapeutic implications.

Methods: This is a prospective single-centre study with the primary objective of characterising resistance mechanisms to osimertinib in advanced EGFR-mutated NSCLC patients treated both in first- and in second-line. Next-Generation Sequencing analysis was conducted on paired tissue biopsies and plasma samples.

Monitoring cfDNA in Plasma and in Other Liquid Biopsies of Advanced EGFR Mutated NSCLC Patients: A Pilot Study and a Review of the Literature.

In order to study alternatives at the tissue biopsy to study EGFR status in NSCLC patients, we evaluated three different liquid biopsy platforms (plasma, urine and exhaled breath condensate, EBC). We also reviewed the literature of the cfDNA biological sources other than plasma and compared our results with it about the sensitivity to EGFR mutation determination. Twenty-two EGFR T790M-mutated NSCLC patients in progression to first-line treatment were enrolled and candidate to osimertinib.

Pneumothorax and pulmonary hemorrhage after CT-guided lung biopsy: incidence, clinical significance and correlation.

Objectives: To evaluate the incidence and clinical significance of pneumothorax (PTX) and pulmonary hemorrhage (PH) after CT-guided lung biopsy (CT-LB). To test correlations of PTX and chest tube insertion (CTI) with PH and other imaging and procedural parameters.

Methods: Pre-procedural CT and CT-LB scans of 904 patients were examined.

Optimizing PD-L1 evaluation on cytological samples from advanced non-small-cell lung cancer.

Programmed cell death-ligand 1 (PD-L1) predicts response to immune checkpoint inhibitors in non-small-cell lung cancer (NSCLC) patients. Most NSCLCs are diagnosed at an advanced stage and using minimally invasive diagnostic procedures that yield small biopsies or cytological samples. Cytological smears and paired histological samples from 52 advanced NSCLC patients were tested for PD-L1 expression by immunocyto/histochemistry (ICC/IHC) and for gene status by FISH.

Transthoracic computed tomography-guided lung biopsy in the new era of personalized medicine.

Computed tomography-guided lung biopsy is a valid and safe procedure for characterizing pulmonary nodules. In the past years, this technique has been mainly used to confirm the malignant nature of undetermined pulmonary lesions; however, today its role has been completely renewed. With the advent of target therapy and immunotherapy, it has arisen for lung cancer, in inoperable patients, the necessity to obtain adequate bioptical material to perform a correct molecular characterization of the lesion.

Looking for Lepidic Component inside Invasive Adenocarcinomas Appearing as CT Solid Solitary Pulmonary Nodules (SPNs): CT Morpho-Densitometric Features and 18-FDG PET Findings.

Objective: To investigate CT morphologic and densitometric features and 18-FDG PET findings of surgically excised lung adenocarcinomas "mixed subtype" with predominant lepidic component, appearing as solid solitary pulmonary nodules (SPNs) on CT scan.

Materials And Methods: Approval for this study was given from each local institutional review board according to its retrospective nature. Nodules pathologically classified as lung adenocarcinoma mixed subtype with bronchioloalveolar otherwise lepidic predominant component, in three different Italian institutions (Napoli; Varese; Parma), were retrospectively selected.

Primary resistance to osimertinib due to SCLC transformation: Issue of T790M determination on liquid re-biopsy.

Objectives: EGFR T790M mutation is the most common mechanism of resistance to first-/second-generation EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) and could be overcome by third-generation EGFR-TKIs, such as osimertinib. Liquid biopsy, a non-invasive technique used to test the presence of the resistant mutation, may help avoiding tissue re-biopsy. However, analysing only circulating-free DNA, information about other less frequent and coexisting resistance mechanisms may remain unrevealed.

Extra-pleuric coaxial system for CT-guided percutaneous fine-needle aspiration biopsy (FNAB) of small (≤20 mm) lung nodules: a novel technique using multiplanar reconstruction (MPR) images.

The aim of the study is to present the diagnostic feasibility, usefulness, and safety of a novel technique for coaxial CT-guided fine-needle aspiration biopsy of small (≤20 mm in diameter) lung nodules. A 18-gauge (G) (1.2 × 40 mm) needle is inserted through the skin in the depth of the thoracic wall tissues remaining outside the pleura.

CT-guided fine-needle aspiration of abdominal and retroperitoneal small lesions with the coaxial technique using MPR images.

Purpose: To demonstrate the advantages of CT-guided fine-needle aspiration (FNA) of abdominal and retroperitoneal small lesions with the coaxial technique using MPR images.

Materials And Methods: The study included retrospectively 50 patients who underwent CT-guided FNA of abdominal and/or retroperitoneal small lesion (<30 mm). Patients with suspected lymphomas or sarcomas were excluded.

Isolation and Characterization of Circulating Tumor Cells in Squamous Cell Carcinoma of the Lung Using a Non-EpCAM-Based Capture Method.

Introduction: The exclusion of circulating tumor cells (CTCs) that have lost epithelial antigens during the epithelial-to-mesenchymal transition (EMT) process by using Epithelial Cell Adhesion Molecule (EpCAM) based capture methods is still a matter of debate. In this study, cells obtained after depletion procedure from blood samples of squamous cell lung cancer (SQCLC) patients were identified based on morphology and characterized with the combination of FISH assessment and immunophenotypic profile.

Materials And Methods: Five mL blood samples, collected from 55 advanced SQCLC patients, were analyzed by a non-EpCAM-based capture method.

ALK and ROS1 rearrangements tested by fluorescence in situ hybridization in cytological smears from advanced non-small cell lung cancer patients.

Background: The identification of ALK and ROS1 rearrangements and the availability of an effective target therapy, such as crizotinib, represent a new option in the treatment of advanced non-small cell lung cancer (NSCLC) patients. In light of recent advances in non-invasive diagnostic procedures, we aimed to demonstrate that direct cytological smears are suitable for assessing ALK and ROS1 rearrangements in patients with NSCLC.

Methods: Fifty-five patients with a cytological diagnosis of lung adenocarcinoma (ADC) were evaluated for ALK rearrangements by fluorescence in situ hybridization (FISH) and 12 patients for ROS1 FISH rearrangements.

Conventional transbronchial needle aspiration with 23 gauge needle: a preliminary study.

Background: Conventional transbronchial needle aspiration (cTBNA) is a safe and minimally invasive procedure with a high yield for the diagnosis of large lymph nodes (LNs) in favourable locations (LNs >1.5 cm in stations #4R and/or #7). However, it is usually underutilized by pulmonologist.

Curved Needles in CT-Guided Fine Needle Biopsies of Abdominal and Retroperitoneal Small Lesions.

Purpose: To demonstrate the advantages of using curved needles in fine needle aspiration (FNA) with CT-guided, for analyzing abdominal and/or retroperitoneal small lesions which are impossible to reach with conventional non-surgical biopsy techniques, particularly in cases in which the cytology sample was not possible to obtain by means of US or CT guide with axial images.

Materials And Methods: An authorization for CT-guided FNA in patients with neoplasms is not required by the institutional review board of our Institute. From April 2012 to November 2014, the study included retrospectively 25 patients (16 M, 9 F) who underwent CT-guided FNA of abdominal and/or retroperitoneal small lesions (<30 mm), in which the ultrasound and axial CT scans were not reliable guides for the biopsy procedure because of the interposition of anatomical obstacles.

CT-guided biopsy of pulmonary nodules: is pulmonary hemorrhage a complication or an advantage?

Purpose: We aimed to assess the correlation between pulmonary hemorrhage and pneumothorax in computed tomography (CT)-guided transthoracic fine needle aspiration (TTFNA), particularly its possible value as protection against the development of pneumotorax.

Materials And Methods: We reviewed the CT images of 538 patients (364 males and 174 females, mean age 70 years, range 36-90 years) who underwent CT-guided TTFNA of pulmonary nodules between January 2008 and September 2013. The following CT findings were assessed: pulmonary hemorrhage (type 1, along the needle track; type 2, perilesional; low-grade, ≤6 mm; high-grade, >6 mm), pneumothorax, distance between the target nodule and the pleural surface, and emphysema.

Predictive factors of diagnostic accuracy of CT-guided transthoracic fine-needle aspiration for solid noncalcified, subsolid and mixed pulmonary nodules.

Purpose: The aim of this study was to analyse factors predicting the diagnostic accuracy of computed tomography (CT)-guided transthoracic fine-needle aspiration (TTFNA) for solid noncalcified, subsolid and mixed pulmonary nodules, with particular attention to those responsible for false negative results with a view to suggesting a method for their correction.

Materials And Methods: From January 2007 to March 2010, we retrospectively reviewed the CT images of 198 patients of both sexes (124 males and 74 females; mean age, 70 years; range age, 44-90) used for the guidance of TTFNA of pulmonary nodules. Aspects considered were: lesion size and density, distance from the pleura, and lesion site.

Reliability of EGFR and KRAS mutation analysis on fine-needle aspiration washing in non-small cell lung cancer.

Introduction: Molecular profiling of advanced non-small cell lung cancer (NSCLC) has become essential for predicting customized medical treatment decision. In light of recent advances in non-invasive diagnostic procedures in NSCLC, we aimed to demonstrate the reliability of assessing molecular tests for epidermal growth factor receptor (EGFR) and KRAS genes on cytological samples by comparing the molecular profile obtained on cells from scraped smears with that on paired needle washing in a series of NSCLC cases.

Methods: Thirty-two cytological specimens obtained by fine-needle aspiration biopsy procedures from primary or metastatic lesions of NSCLCs were Giemsa stained for a rapid on-site evaluation and, in case of an adequate sampling, the cellular material obtained from needle washing was collected into a saline solution.

Preoperative diagnosis of THYR 3 versus follicular lesion: malignant postoperative ratio.

Aim: In the evaluation of nodular thyroid lesions, cytology is the main diagnostic instrument, associated with ultrasound examination.

Methods: We prospectively categorized into a dedicated database, 612 patients submitted to thyroidectomy from January 2009 to December 2011. We selected two groups of patients: the cases with "follicular lesions" and the cases classified as "THYR 3" using Bethesda Classification.

Multinational study of oestrogen and progesterone receptor immunocytochemistry on breast carcinoma fine needle aspirates.

Objectives: To collect data on the variability of immunocytochemical (ICC) procedures used to detect oestrogen/progesterone receptors (ER/PR) on cytological material; to test the reproducibility of results; and to identify the crucial points in the ICC procedures that affect the result.

Methods: Ten laboratories from eight countries participated in a two-part study. In the first part, one of the participants (the coordinator) prepared and distributed cytospins from a fine needle aspirate of a primary breast carcinoma.

Epidermal growth factor receptor and Kras gene expression: reliability of mutational analysis on cytological samples.

Epidermal growth factor receptor (EGFR) and Kras gene mutations are crucial for discriminating patients responsive to anti-EGFR drugs in non-small cell lung cancer (NSCLC) and colorectal cancer (CRC), respectively. The majority of NSCLCs come to clinical attention at an advanced stage when surgery is no longer recommended and a considerable number of them are diagnosed by cytology only. A large number of metastatic CRCs are also diagnosed by imaging and minimally invasive techniques such as fine-needle aspiration biopsy.

Endometrial metastasis of lung adenocarcinoma: a case report.

The female genital tract is an infrequent site of metastasis, in particular from extragenital primary tumors such as non-small cell lung cancer. Ovarian metastases have been described as disseminations of lung adenocarcinoma; rare cases of secondary localizations in adnexa, cervix and vagina were also observed in the literature, but none of these had endometrial involvement. We report the first case, to our knowledge, of non-small cell lung cancer with metastatic spread to the endometrium.

Comparison of HER2 status in primary and paired metastatic sites of gastric carcinoma.

Background: Trastuzumab has recently shown efficacy in the treatment of HER2-positive advanced gastric adenocarcinoma. Although antibody-based therapies target the metastatic disease, HER2 status is usually evaluated in the primary tumour because metastatic sites are rarely biopsied. The aim of this study was to compare HER2 status in primary and paired metastatic sites of gastric adenocarcinoma.

Accuracy of fine needle aspiration cytology in the pathological typing of non-small cell lung cancer.

Background: Histological typing of non-small cell lung cancer (NSCLC) has an increasing clinical relevance due to the emerging differences in medical treatment between squamous and nonsquamous tumors. However, most NSCLCs are diagnosed in an advanced stage, and the diagnosis is often obtained exclusively by cytology either exfoliative or following fine needle aspiration. We investigated the accuracy of fine needle aspiration cytology (FNAC) in NSCLC typing as compared with histology.

Can misdiagnosis in pre-operative FNAC of thyroid nodule influence surgical treatment?

Background: Pre-operative cytology in thyroid disease remains the most appropriate diagnostic test for defining the nature of a thyroid nodule before surgical excision.

Materials And Methods: We selected the most recent 825 surgical thyroid procedures performed in our institution from January 2004 to June 2007; 776 were total thyroidectomies, 23 were lobe-isthmectomies, and 26 were radical neck dissections. We distributed the data based on pre-operative cytology.