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

Aim: 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. Methods: Cytological smears and paired histological samples from 52 advanced NSCLC patients were tested for PD-L1 expression by immunocyto/histochemistry (ICC/IHC) and for PD-L1 gene status by FISH. Results: PD-L1 was overexpressed in 9/52 (17%) cytological samples and in seven (13.5%) matched biopsies. The concordance between immunocytochemistry and IHC was 92.3% (48/52; p < 0.001). The concordance between PD-L1 gene status on cytology and histology was 69.2% (18/26; p < 0.001). No correlation between IHC and fluorescence in situ hybridization results was found. Conclusion: Our data support the feasibility and reliability of PD-L1 protein and PD-L1 gene assessment on direct cytological smears from NSCLC patients whenever histological sample are inadequate

A prospective study

Background: Conventional methods used for diagnosis of lung cancer are still inadequate for objectively estimating the exact depth of tumor invasion to bronchial wall, nodal staging, infiltration of mediastinal structures and extent of early lung cancer. Endobronchial ultrasound (EBUS) was introduced into clinical hospital practice in 2000, as a new diagnostic procedure visualizing bronchial and peribronchial tumors, mediastinal lymph nodes and adjacent vascular structures, with the aim of assessing bronchial wall and extraluminal pathology. Purpose: Since major European publications deal with EBUS application in general anesthesia, its use in routine bronchoscopy under topical anesthesia has been addressed more closely in this study. Hence the primary question we attempted to answer has been, is the addition of EBUS under topical anesthesia to bronchoscopy practicable and does it improve diagnosis in bronchial cancer beyond computer tomography (CT) and bronchoscopy alone? Patients, materials & methods: 50 consecutive patients were recruited with suspected lung cancer (suspicious shadow(s) and / or mediastinal adenopathy in chest CT) undergoing diagnostic and/or staging flexible fiberoptic bronchoscopy. In all patients, EBUS was performed as an adjuvant to bronchoscopy using midazolam sedation, lidocaine mucosal anesthesia and supplemental oxygen. A 20-mega Hz radial mechanical ultrasound probe integrated with a balloon, connected to ultrasound unit is advanced through the 2.8-millimeter working channel FFB to area of interest, where the balloon is inflated to provide a medium for ultrasound transmission. Agreement of EBUS findings with FFB/ CT and cyto-histology, additional information provided by EBUS, complications, patients tolerability under topical anesthesia were assessed. Results: Out of the 50 cases with suspected lung cancer, 36 cases were pathologically verified. In 36 lung cancer cases, EBUS findings coincided with those of FFB and CT in main features of the disease process. EBUS provided additional information in 25 cases (69%), in which 20 additive lymph nodes were detected; depth of tumor invasion was determined in 18 cases and compression of pulmonary arteries in 2 cases. In addition, it was helpful in explanation of bronchoscopic findings in 19 cases (53%) and exclusion of mediastinal structures infiltration. On the other hand, FFB and CT provided additional information in 7 cases (19%). In all studied cases, EBUS assisted transbronchial needle aspiration biopsy had diagnostic yield in extraluminal lesions up to 89% and 90% in mediastinal and intrapulmonary adenopathy. EBUS addition could change the nodal descriptors in 4 cases and patient stage in 2 cases, but without any subsequent therapeutic consequences. The complications encountered in all studied cases were either mild (6) or moderate (1) desaturation, mild (9) or moderate (3) cough and 2 cases of tachycardia. The procedure is completely tolerated by most of the patients (66%). There is an average increase in examination time of 15 minutes, constituting 44% of total time of bronchoscopy. Conclusions: EBUS application under topical anesthesia is a well-tolerated procedure, associated with mild infrequent side effects, providing valuable beneficial additional information to bronchoscopy and CT; hence its addition can improve the diagnosis and assessment of bronchial cancer. Further expected technical improvements are still needed, which may allow EBUS in the near future to play a more important role in diagnostic and interventional bronchoscopy. Recommendations: Prospective multicentre studies are needed for critical assessment of EBUS in operable lung cancer patients, correlating EBUS image findings with postoperative anatomical and pathological findings in same areas examined. A more applicable definition of depth of tumor invasion, the use of 30 MHz probes, the use of double lumen bronchoscopy, the cost effectiveness of procedure and the role of EBUS in peripheral lesions are recommended to be further studied. The sound indications of this new technology need to be settled, in the diagnostic investigation path of lung cancer

Recent Advances and Researches in the Field of Fine Needle Aspiration Cytopathology

Fine needle aspiration cytology/biopsy (FNAB) is quite often one of the first tests for the initial evaluation of lesions/swellings which are accessible to the needle tracts. The technique has its limitations in certain cases owing to the non-representative or inadequate material aspirated or due to the confusion arising from the lack of histologic pattern as observed on a biopsy. An immediate rapid on-site evaluation (ROSE) is valuable in minimizing the limitations arising from the non-representative/inadequate material. The introduction and application of several ancillary modalities, like immunocytochemistry, molecular tests and the advancements in interventional radiology, has further revolutionized the diagnostic scope of FNA biopsy. Molecular tests on the FNAC samples can aid in the distinction of benign from malignant lesions, in determining the genetic abnormalities and genetic makeup of tumors that can be useful not only for making a more specific diagnosis but also for determining prognosis, response to therapy and for the selection of patients for targeted therapy. FNAB biopsies have an added advantage in comparison with the core needle biopsies for molecular analysis since they have a much lower contamination of stroma. The chapter will be discussing the advancements and the uses of these ancillary techniques in the field of FNAC

Navigational bronchoscopy for early lung cancer: a road to therapy

Peripheral lung nodules remain challenging for accurate localization and diagnosis. Once identified, there are many strategies for diagnosis with heterogeneous risk benefit analysis. Traditional strategies such as conventional bronchoscopy have poor performance in locating and acquiring the required tissue. Similarly, while computerized-assisted transthoracic needle biopsy is currently the favored diagnostic procedure, it is associated with complications such as pneumothorax and hemorrhage. Video-assisted thoracoscopic and open surgical biopsies are invasive, require general anesthesia and are therefore not a first-line approach. New techniques such as ultrathin bronchoscopy and image-based guidance technologies are evolving to improve the diagnosis of peripheral lung lesions. Virtual bronchoscopy and electromagnetic navigation systems are novel technologies based on assisted-computerized tomography images that guide the bronchoscopist toward the target peripheral lesion. This article provides a comprehensive review of these emerging technologies

Diagnostic procedures for non-small-cell lung cancer (NSCLC): recommendations of the European Expert Group

Background There is currently no Europe-wide consensus on the appropriate preanalytical measures and workflow to optimise procedures for tissue-based molecular testing of non-small-cell lung cancer (NSCLC). To address this, a group of lung cancer experts (see list of authors) convened to discuss and propose standard operating procedures (SOPs) for NSCLC. Methods Based on earlier meetings and scientific expertise on lung cancer, a multidisciplinary group meeting was aligned. The aim was to include all relevant aspects concerning NSCLC diagnosis. After careful consideration, the following topics were selected and each was reviewed by the experts: surgical resection and sampling; biopsy procedures for analysis; preanalytical and other variables affecting quality of tissue; tissue conservation; testing procedures for epidermal growth factor receptor, anaplastic lymphoma kinase and ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) in lung tissue and cytological specimens; as well as standardised reporting and quality control (QC). Finally, an optimal workflow was described. Results Suggested optimal procedures and workflows are discussed in detail. The broad consensus was that the complex workflow presented can only be executed effectively by an interdisciplinary approach using a well-trained team. Conclusions To optimise diagnosis and treatment of patients with NSCLC, it is essential to establish SOPs that are adaptable to the local situation. In addition, a continuous QC system and a local multidisciplinary tumour-type-oriented board are essential

A Study of solitary pulmonary nodule in 50 cases

54% of Solitary Pulmonary Nodule in the study was malignant. 26% cases were of infective origin – tuberculosis and pneumonia / lung abscess. 14% cases were benign and 6% were indeterminate lesion. • 48% of the malignancies were squamous cell carcinoma, 33% were adenocarcinoma and 10% were small cell carcinoma. • Commonest malignancy in SPN was squamous cell carcinoma. Inordinately high number of smokers in study population probably predisposed to higher incidence of squamous cell carcinoma. • Symptoms and signs were not conclusive. 50% cases were asymptomatic or had vague ill-health. 40% had cough with or without sputum. Minimal non-specific lung signs (50%) or no elicitable physical sign (25%) were predominant findings. • 22% cases only could be diagnosed early enough for a favourable treatment response. • Exclusively males were found to have malignancy in SPN, though female sample size was very low (no. 2) in this study. • 72% of SPNs above 60 yrs of age were malignant. But even at age 25 yrs, Small Cell Carcinoma has developed. • 82% of study population were smokers, 81% of > 40 pack yrs smokers had developed malignancy. • 18% of SPNs were diabetics and were mostly having infective pathology. • Most important characteristic feature of SPN is margin and size of the lesion in x – ray. • 94% of spiculated margin and 72% of size >4 cm diameter nodules were malignant. 88% of <3cm nodules were benign/infective origin. • 65% of nodules with contrast enhancement of > 20 HU in CT were malignant. • 2 cases of indeterminate pathology could be diagnosed of benign pathology only on basis of benign pattern of doubling time. • Both transthoracic aspiration cytology / biopsy and fibre – optic bronchoscopy and lavage / brushing / biopsy were important diagnostic tools in carefully selected patients with yield of > 80%. Overall, transthoracic aspiration cytology / biopsy were slightly more efficacious as a diagnostic measure. • Fine needle aspiration cytology / biopsy of lymph nodes were conclusive in palpable lymph nodes