A Case of Anti-SAE1 Dermatomyositis.

Introduction: Anti-SAE1 antibodies have a low prevalence in dermatomyositis patients. Case Description. A 61-year-old woman presented with progressive shortness of breath, arthralgia, heliotrope rash, Gottron's papules, and erythematous rash. She had an interstitial lung disease (ILD) with a significant decrease in lung function. There was no muscle involvement. Immunological laboratory test results showed strongly positive anti-SAE1 antibodies. Glucocorticoid treatment resulted in remission of dermatomyositis. Conclusion: Anti-SAE antibodies in dermatomyositis patients are closely linked to unique clinical features.

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.

[Fatal interstitial lung disease associated with erlotinib use]. / Fataal interstitieel longbeeld bij erlotinib-gebruik.

BACKGROUND: Erlotinib is used to treat patients with non-small cell lung cancer (NSCLC). The use of this tyrosine kinase inhibitor can result in interstitial lung disease, but the aetiology of this phenomenon is not clear. CASE DESCRIPTION: A 68-year-old man with NSCLC, who had been undergoing treatment with erlotinib (150 mg daily) for the previous two weeks, presented with dyspnoea. A chest x-ray revealed infiltrates for which we started broad-spectrum antibiotics, high dose glucocorticoids and oxygen supplementation; erlotinib was discontinued. Despite these measures, the patient died of respiratory failure. Autopsy showed diffuse alveolar damage; the blood cultures taken while the patient was still alive and the post-mortem lung cultures were negative. The alveolar damage was possibly a consequence of the use of erlotinib. CONCLUSION: Clinicians should be alert to worsening pulmonary symptoms without signs of infection in patients using erlotinib. Discontinuation of erlotinib and glucocorticoid treatment should be considered until alveolar damage caused by the use of erlotinib can be excluded.