Utility of bronchoscopically obtained frozen cytology pellets for next-generation sequencing.

BACKGROUND: Next-generation sequencing (NGS) is essential for lung cancer treatment. It is important to collect sufficient tissue specimens, but sometimes we cannot obtain large enough samples for NGS analysis. We investigated the yield of NGS analysis by frozen cytology pellets using an Oncomine Comprehensive Assay or Oncomine Precision Assay. METHODS: We retrospectively enrolled patients with lung cancer who underwent bronchoscopy at Kobe University Hospital and were enrolled in the Lung Cancer Genomic Screening Project for Individualized Medicine. We investigated the amount of extracted DNA and RNA and determined the NGS success rates. We also compared the amount of DNA and RNA by bronchoscopy methods. To create the frozen cytology pellets, we first effectively collected the cells and then quickly centrifuged and cryopreserved them. RESULTS: A total of 132 patients were enrolled in this study between May 2016 and December 2022; of them, 75 were subjected to frozen cytology pellet examinations and 57 were subjected to frozen tissue examinations. The amount of DNA and RNA obtained by frozen cytology pellets was nearly equivalent to frozen tissues. Frozen cytology pellets collected by endobronchial ultrasound-guided transbronchial needle aspiration yielded significantly more DNA than those collected by transbronchial biopsy methods. (P < 0.01) In RNA content, cytology pellets were not inferior to frozen tissue. The success rate of NGS analysis with frozen cytology pellet specimens was comparable to the success rate of NGS analysis with frozen tissue specimens. CONCLUSIONS: Our study showed that frozen cytology pellets may have equivalent diagnostic value to frozen tissue for NGS analyses. Bronchial cytology specimens are usually used only for cytology, but NGS analysis is possible if enough cells are collected to create pellet specimens. In particular, the frozen cytology pellets obtained by endobronchial ultrasound-guided transbronchial needle aspiration yielded sufficient amounts of DNA. TRIAL REGISTRATION: This was registered with the University Medical Hospital Information Network in Japan (UMINCTR registration no. UMIN000052050).

TAPO in first-line osimertinib therapy and continuation of osimertinib.

BACKGROUND: Osimertinib is associated with a relatively high frequency of drug-induced interstitial lung disease (D-ILD), and transient asymptomatic pulmonary opacities (TAPO) have been reported to occur during osimertinib administration. The frequency of TAPO during first-line treatment and the pros and cons of osimertinib continuation is unknown. METHODS: This was a multicenter, retrospective study. The purpose of this study was to research the frequency of TAPO and to evaluate osimertinib continuation in first-line therapy. We also evaluated progression-free survival (PFS) including subgroup analysis. RESULTS: From August 2018 to December 2020, 133 patients were enrolled into the study. The median observation period was 23.2 months (0.3-48.3 months). Thirty patients (22.6%) experienced D-ILD events, including 16 patients (12.1%) with CTCAE grade 1, five patients (3.8%) with grade 2, and nine patients (6.7%) with grade 3 and above D-ILD. Among the patients with grade 1 D-ILD, 11 cases (8.3%) of TAPO were observed, and all patients succeeded in osimertinib continuation. The TAPO images were characterized by localized patchy opacities (73%). The median PFS was 22.6 months (95% confidence interval [CI]: 17.8-28.7 months). Patients with TAPO had a significantly longer PFS than patients with non-TAPO D-ILD in the multivariate analysis. CONCLUSIONS: This study showed that grade 1 D-ILD might include TAPO and that patients with TAPO might have good PFS. We need to consider the possibility of osimertinib continuation when lung opacities appear.

Postmortem Diagnosis of Gallbladder Cancer Presenting as Pulmonary Lymphangitic Carcinomatosis With Concurrent Gallbladder Adenomyomatosis.

In pulmonary lymphangitic carcinomatosis, it can be difficult to identify the primary site of the cancer on computed tomography (CT) imaging. Here, we report a rare case of pulmonary lymphangitic carcinomatosis, which was difficult to diagnose as gallbladder cancer. An 81-year-old woman, previously followed up for gallbladder adenomyomatosis, presented with persistent cough. CT revealed multiple small nodular opacities, irregular interlobular septal thickening, and bilateral pleural effusions. Based on the CT findings and the presence of malignant cells in the pleural fluid, a presumptive diagnosis of pulmonary lymphangitic carcinomatosis was made, but the primary site was not identified. The patient died of respiratory failure in two months. Autopsy confirmed gallbladder cancer with pulmonary lymphangitic carcinomatosis and multiorgan metastasis. Clinicians should be aware that in patients with gallbladder adenomyomatosis, gallbladder cancer can present with rapidly progressive respiratory symptoms even in the absence of an evident mass or increased gallbladder wall thickening.

Endobronchial metastases 20 years after prostate cancer excision.

A 78-year-old Japanese man who had undergone total prostatectomy for prostate cancer (pT3cN1M0, Gleason score 3 + 3) 20 years previously was referred to the Respiratory Medicine Department of our institution because of a 1-week history of chest pain and cough. Computed tomography showed multiple small nodules and mediastinal lymph node enlargement. Bronchoscopy revealed multiple soft polypoid masses and obstruction of the lingular segment. Prostate-specific antigen (PSA) concentrations had increased markedly from 0.48 ng/mL in 2014 to 741 ng/mL in 2018. The diagnosis of prostatic cancer metastases was confirmed by revealing the presence of PSA via immunohistological staining of a bronchoscopically obtained biopsy of one of the masses. The patient had not been attending scheduled follow-up visits for the past 4 years. Treatment with degarelix (a gonadotropin-releasing hormone) was started, and the PSA concentration decreased dramatically (29 ng/mL). Metastases from prostate cancer are rarely first diagnosed two decades after radical prostatectomy. This patient illustrates the importance of obtaining a complete medical history.