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Objectives: Tumor programmed death ligand 1 (PD-L1) expression is associated with improved clinical benefit from immunotherapies targeting the PD-1 pathway. We conducted a global, multicenter, retrospective observational study to determine real-world prevalence of tumor PD-L1 expression in patients with NSCLC., Materials and Methods: Patients ≥18 years with histologically confirmed stage IIIB/IV NSCLC and a tumor tissue block (≤5 years old) obtained before treatment were identified in 45 centers across 18 countries. Tumor samples from eligible patients were selected consecutively, when possible. PD-L1 expression was evaluated at each center using the PD-L1 IHC 22C3 pharmDx kit (Agilent, Santa Clara, CA, USA)., Results: Of 2617 patients who met inclusion criteria, 2368 (90%) had PD-L1 data; 530 (22%) patients had PD-L1 TPS ≥ 50%, 1232 (52%) had PD-L1 TPS ≥ 1%, and 1136 (48%) had PD-L1 TPS < 1%. The most common reason for not having PD-L1 data (n = 249) was insufficient tumor cells (<100) on the slide (n = 170 [6%]). Percentages of patients with PD-L1 TPS ≥ 50% and TPS ≥ 1%, respectively were: 22%/52% in Europe; 22%/53% in Asia Pacific; 21%/47% in the Americas, and 24%/55% in other countries. Prevalence of EGFR mutations (19%) and ALK alterations (3%) was consistent with prior reports from metastatic NSCLC studies. Among 1064 patients negative for both EGFR mutation and ALK alteration, the percentage with PD-L1 TPS ≥ 50% and TPS ≥ 1%, respectively, were 27% and 53%., Conclusions: This is the largest real-world study in advanced NSCLC to date evaluating PD-L1 tumor expression using the 22C3 pharmDx kit. Testing failure rate was low with local evaluation of PD-L1 TPS across a large number of centers. Prevalence of PD-L1 TPS ≥ 50% and TPS ≥ 1% among patients with stage IIIB/IV NSCLC was similar across geographic regions and broadly consistent with central testing results from clinical trial screening populations., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Rationale: Conventional transbronchial needle aspiration (TBNA) and endobronchial ultrasound (EBUS)-TBNA are widely accepted tools for the diagnosis and staging of lung cancer and the initial procedure of choice for staging. Obtaining adequate specimens is key to provide a specific histologic and molecular diagnosis of lung cancer., Objectives: To develop practice guidelines on the acquisition and preparation of conventional TBNA and EBUS-TBNA specimens for the diagnosis and molecular testing of (suspected) lung cancer. We hope to improve the global unification of procedure standards, maximize the yield and identify areas for research., Methods: Systematic electronic database searches were conducted to identify relevant studies for inclusion in the guideline [PubMed and the Cochrane Library (including the Cochrane Database of Systematic Reviews)]., Main Results: The number of needle aspirations with both conventional TBNA and EBUS-TBNA was found to impact the diagnostic yield, with at least 3 passes needed for optimal performance. Neither needle gauge nor the use of miniforceps, the use of suction or the type of sedation/anesthesia has been found to improve the diagnostic yield for lung cancer. The use of rapid on-site cytology examination does not increase the diagnostic yield. Molecular analysis (i.e. EGFR, KRAS and ALK) can be routinely performed on the majority of cytological samples obtained by EBUS-TBNA and conventional TBNA. There does not appear to be a superior method for specimen preparation (i.e. slide staining, cell blocks or core tissue). It is likely that optimal specimen preparation may vary between institutions depending on the expertise of pathology colleagues., (© 2014 S. Karger AG, Basel.)

Objective: Endoscopic ultrasound (EUS)-guided Trucut biopsy (EUS-TCB) has recently emerged as a method that seeks to overcome the limitations of EUS-guided fine needle aspiration (EUS-FNA) by providing a core-tissue specimen needed to increase the yield and accuracy of the diagnosis. The aim of our study was to evaluate whether EUS-TCB adds any information to EUS-FNA in selected patients and to assess the diagnostic yield, overall accuracy and complications of EUS-TCB as compared with EUS-FNA., Material and Methods: The study prospectively included 30 patients who had undergone both procedures., Results: The yield of adequate tissue harvesting was similar for EUS-FNA and EUS-TCB (96.4% versus 89.3%, p=NS), with the same number of passes done. The diagnostic accuracy of EUS-FNA was also similar to that of EUS-TCB for the diagnosis of malignant mediastinal masses (73.7% versus 68.4%, p=NS). However, the accuracy for obtaining a specific diagnosis was significantly lower for EUS-FNA compared with EUS-TCB (5.3% and 68.4%, p<0.005). EUS-TCB did not appear to help as a rescue procedure in mediastinal tumours, after a false negative result of EUS-FNA. All cases of submucosal tumours were correctly classified by EUS-TCB as gastrointestinal stromal cell tumours (GISTs) or leiomyomas, while EUS-FNA raised only a suspicion of mesenchymal tumour., Conclusions: EUS-TCB was certainly useful when immunohistochemistry was needed, for example in submucosal tumours and lymphoma, as well as to confirm and characterize the primary or metastatic origin of mediastinal masses. The information provided by EUS-FNA and EUS-TCB is complementary, especially in selected cases where a complete histological diagnosis has an important impact on the clinical management.

A sandwich-type ELISA has been developed for the assessment of complexes between urokinase-type plasminogen activator (uPA) and its receptor (uPAR) in extracts of squamous cell lung carcinomas. The assay is based on a combination of rabbit polyclonal anti-uPA antibodies and a biotinylated mouse anti-uPAR monoclonal antibody (MAb). The detection limit of the assay is approximately 0.5 fmol/ml. A linear dose-response is obtained with up to 40 fmol/ml of uPA:uPAR complexes, while uPA and uPAR separately do not cause any response in the ELISA. A buffer which has been used previously for optimal extraction of uPAR yields the highest amounts of uPA:uPAR complexes. Absorption of tumor extracts with anti-uPA or anti-uPAR MAbs results in a complete disappearance of the ELISA signal, demonstrating the specificity of the ELISA. The recovery of chemically cross-linked uPA:uPAR complexes added to tumor extracts varies between 80% and 105%. The intra- and inter-assay variation coefficients are 5.3% and 9.8%, respectively. Furthermore, a peptide antagonist for uPAR was employed to evaluate de novo uPA:uPAR complex formation during tumor tissue extraction and the immunoassay procedure. Our results strongly indicate that de novo complex formation is a major factor to consider and that complexes analyzed in the presence of this antagonist represent original uPA:uPAR complexes present prior to tumor tissue processing. The present ELISA appears suitable for studying the potential prognostic impact of uPA:uPAR complexes in lung tumor tissue as well as other types of cancer.

Carcinoid tumor of the middle ear is a very rare benign neoplasm, which may be mistaken for a malignant tumor. We present two new cases together with a review of 28 previously reported cases. Nearly all patients had progressive hearing loss, most often of the conductive type. About half of the patients complained of tinnitus and fullness of the ear. The typical otoscopic picture was erythema or lateral bulging of the tympanic membrane, which was intact in most patients. The tumor was most often localized to the middle ear with varying degree of extensions into neighboring areas. It often encapsulated the ossicles, which sometimes were eroded. Systemic symptoms were only reported in two cases. The tumor is clinically benign and total excision of the tumor and affected ossicles is an adequate treatment. The correct diagnosis, which should be considered in case of any adenomatous tumor of the middle ear, requires immunohistochemical and ultrastructural procedures.

A one-year-old child had hypertrophy of the left leg and an unusual constellation of a naevus flammeus and superficial enlarged veins of the trunk together with successive appearance and involution since birth of numerous nodular elements located in the naevus and in the surrounding normal skin. Microscopic examination of these elements showed haemangiomas with capillaries, cavernous channels and lymphangiomatous components. The benign nature of transient nodular elements located to the trunk and the lack of associated visceral vascular malformations in the Klippel-Trénaunay syndrome are documented.