Endobronchial ultrasound in diagnosing and staging of lung cancer by Acquire 22G TBNB versus regular 22G TBNA needles: A randomized clinical trial.

OBJECTIVES: Endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) has an important role in the diagnosis and staging of lung cancer. Evaluation of programmed death ligand 1 (PD-L1) expression and molecular profiling has become standard of care but cytological samples frequently contain insufficient tumor cells. The 22G Acquire needle with Franseen needle tip was developed to perform transbronchial needle biopsy (TBNB) with improved tissue specimens. This study evaluated if the 22G Acquire TBNB needle results in enhanced PD-L1 suitability rate compared to the regular Expect 22G TBNA needle. METHODS: in this multi-center randomized clinical trial (Netherlands Trial Register NL7701), patients with suspected (N)SCLC and an indication for mediastinal/hilar staging or lung tumor diagnosis were recruited in five university and general hospitals in the Netherlands, Poland, Italy and Czech Republic. Patients were randomized (1:1) between the two needles. Two blinded reference pathologists evaluated the samples. The primary outcome was PD-L1 suitability rate in patients with a final diagnosis of lung cancer. In case no malignancy was diagnosed, the reference standard was surgical verification or 6 month follow-up. RESULTS: 154 patients were randomized (n = 76 Acquire TBNB; n = 78 Expect TBNA) of which 92.9% (n = 143) had a final malignant diagnosis. Suitability for PD-L1 analysis was 80.0% (n = 56/70; 95 %CI 0.68-0.94) with the Acquire needle and 76.7% (n = 56/73; 95 %CI 0.65-0.85) with the Expect needle (p = 0.633). Acquire TBNB needle specimens provided more frequent superior quality (65.3% (95 %CI 0.57-0.73) vs 49.4% (95 %CI 0.41-0.57, p = 0.005) and contained more tissue cores (72.0% (95 %CI 0.60-0.81) vs 41.0% (95 %CI 0.31-0.54, p < 0.01). There were no statistically significant differences in tissue adequacy, suitability for molecular analysis and sensitivity for malignancy and N2/N3 disease. CONCLUSION: The 22G Acquire TBNB needle procured improved quality tissue specimens compared to the Expect TBNA needle but this did not result in an improved the suitability rate for PD-L1 analysis.

Position dependent dyspnea and hypoxemia.

A 63-year-old man was analyzed for platypnea-orthodeoxia syndrome (POS). A complete obstruction due to bronchial carcinoma was found in the left main bronchus with bronchoscopy. After left sided pneumonectomy POS resolved completely. Historical reports suggest increased shunting through the left lung could occur in the upright position caused by decreased compression of the left pulmonary artery due to the central bronchial carcinoma. Partially absent hypoxic vasoconstriction was confirmed in this case and suggests (without a relevant shunt through a patent foramen ovale) this 'historical' hypothesis could explain the POS due to increased shunting in the upright position in this patient.

Inflammatory myofibroblastic tumor of the lung: A rare endobronchial mass.

A 42-year old male was referred with a 6-week history of new onset dyspnea. The patient had normal vital signs, no relevant medical history and the only abnormality was a left sided inspiratory wheeze. No abnormalities were seen on the chest X-ray. A bronchoscopy was performed which showed a well-circumscribed hypervasculated mass in the left main bronchus. A biopsy was taken, which was complicated after the procedure by dislocation of the mass and coughed up by the patient. Both samples were send for pathologic review. A contrast CT was performed which showed a localized remaining mass in the left main bronchus and no lymph node involvement. Pathological evaluation showed spindle-shaped cell proliferation with mitotic activity in the second larger tissue which could be consistent with an inflammatory myofibroblastic tumor (IMT), whereas the first biopsy sample only showed granulomatous inflammation. Following multidisciplinary review the diagnosis of IMT was made and a treatment plan was decided. Because of the localized position of the mass the patient was treated with laser coagulation via rigid bronchoscopy instead of surgery. Bronchoscopic review afterwards showed complete resolution of the mass and the dyspnea had resolved. This case highlights the difficulty of making the IMT-diagnosis and the option of treating it with laser coagulation via rigid bronchoscopy.

Optimizing Mutation and Fusion Detection in NSCLC by Sequential DNA and RNA Sequencing.

INTRODUCTION: Frequently, patients with locally advanced or metastatic NSCLC are screened for mutations and fusions. In most laboratories, molecular workup includes a multitude of tests: immunohistochemistry (ALK, ROS1, and programmed death-ligand 1 testing), DNA sequencing, in situ hybridization for fusion, and amplification detection. With the fast-emerging new drugs targeting specific fusions and exon-skipping events, this procedure harbors a growing risk of tissue exhaustion. METHODS: In this study, we evaluated the benefit of anchored, multiplexed, polymerase chain reaction-based targeted RNA sequencing (RNA next-generation sequencing [NGS]) in the identification of gene fusions and exon-skipping events in patients, in which no pathogenic driver mutation was found by DNA-based targeted cancer hotspot NGS (DNA NGS). We analyzed a cohort of stage IV NSCLC cases from both in-house and referral hospitals, consisting 38.5% cytology samples and 61.5% microdissected histology samples, mostly core needle biopsies. We compared molecular findings in a parallel workup (DNA NGS and RNA NGS, cohort 1, n = 198) with a sequential workup (DNA NGS followed by RNA NGS in selected cases, cohort 2, n = 192). We hypothesized the sequential workup to be the more efficient procedure. RESULTS: In both cohorts, a maximum of one oncogenic driver mutation was found per case. This is in concordance with large, whole-genome databases and suggests that it is safe to omit RNA NGS when a clear oncogenic driver is identified in DNA NGS. In addition, this reduced the number of necessary RNA NGS to only 53% of all cases. The tumors of never smokers, however, were enriched for fusions and exon-skipping events (32% versus 4% in former and current smokers, p = 0.00), and therefore benefited more often from the shorter median turnaround time of the parallel approach (15 d versus only 9 d in the parallel workup). CONCLUSIONS: We conclude that sequentially combining DNA NGS and RNA NGS is the most efficient strategy for mutation and fusion detection in smoking-associated NSCLC, whereas for never smokers we recommend a parallel approach. This approach was shown to be feasible on small tissue samples including for cytology tests, can drastically reduce the complexity and cost of molecular workup, and also provides flexibility in the constantly evolving landscape of actionable targets in NSCLC.

[A 24-year-old man with chest pain]. / Een 24-jarige man met pijn op de borst.

A 24-year-old man was seen with position dependent chest pain and fever. Electrocardiography showed typical diffuse repolarisation changes matching with perimyocarditis. Local petechiae developed on the left leg and bloodcultures were positive for Neisseria meningitidis serogroup C, which provided the diagnosis perimyocarditis caused by Neisseria meningitidis.