Comparison of the specimen quality of endobronchial ultrasound-guided intranodal forceps biopsy using standard-sized forceps versus mini forceps for lung cancer: A prospective study.

BACKGROUND AND OBJECTIVE: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a diagnostic procedure with adequate performance; however, its ability to provide specimens of sufficient quality and quantity for treatment decision-making in advanced-stage lung cancer may be limited, primarily due to blood contamination. The use of a 0.96-mm miniforceps biopsy (MFB) permits true histological sampling, but the resulting small specimens are unsuitable for the intended applications. Therefore, we introduced a 1.9-mm standard-sized forceps biopsy (SFB) and compared its utility to that of MFB. METHODS: We prospectively enrolled patients from three institutions who presented with hilar/mediastinal lymphadenopathy and suspected advanced-stage lung cancer, or those who were already diagnosed but required additional tissue specimens for biomarker analysis. Each patient underwent MFB followed by SFB three or four times through the tract created by TBNA using a 22-gauge needle on the same lymph node (LN). Two pathologists assessed the quality and size of each specimen using a virtual slide system, and diagnostic performance was compared between the MFB and SFB groups. RESULTS: Among the 60 enrolled patients, 70.0% were diagnosed with adenocarcinoma. The most frequently targeted sites were the lower paratracheal LNs, followed by the interlobar LNs. The diagnostic yields of TBNA, MFB and SFB were 91.7%, 93.3% and 96.7%, respectively. The sampling rate of high-quality specimens was significantly higher in the SFB group. Moreover, the mean specimen size for SFB was three times larger than for MFB. CONCLUSION: SFB is useful for obtaining sufficient qualitative and quantitative specimens.

Adenocarcinoma originating in the anterior mediastinum diagnosed by endobronchial ultrasound-guided transbronchial cryobiopsy: a case report.

BACKGROUND: Endobronchial ultrasound-guided transbronchial cryobiopsy (EBUS-cryobiopsy) is advantageous for collecting larger specimens with minimal crushing; however, it has not been widely used for mediastinal tumors. CASE PRESENTATION: A 73-year-old woman with a history of left breast cancer underwent surgery followed by radiotherapy. Computed tomography showed a mass in the anterior mediastinum that was in extensive contact with the sternum on the ventral side and partly with the trachea on the dorsal side. Two computed tomography-guided needle biopsies (CTNBs) were performed on the mass; however, a definitive diagnosis was not made because of severe crush artifacts. Subsequently, we performed EBUS-cryobiopsy and safely obtained sufficient specimen volume with minimal crushing. The histopathological diagnosis was adenocarcinoma, with immunobiological features distinct from those of previous breast cancers. Her overall diagnosis was a rare tumor originating in the anterior mediastinum. CONCLUSIONS: EBUS-cryobiopsy can be safely performed in narrow areas surrounded by major blood vessels, and the obtained specimens may be superior to CTNBs for histopathological diagnosis.

Suitability of respiratory endoscopy for sampling malignant thoracic tumors for comprehensive genomic profiling.

Comprehensive genomic profiling (CGP) is implemented to detect actionable gene aberrations and design matched therapies. Although malignant thoracic tumors are commonly detected through respiratory endoscopy, it is questionable whether the small specimens obtained thereof are sufficient for CGP. Therefore, this study aimed to investigate the suitability of respiratory endoscopy for sampling primary and metastatic thoracic tumors for CGP. Patients whose specimens were collected through respiratory endoscopy and assessed by pathologists to determine their suitability for CGP at our institution between June 2019 and May 2022 were reviewed retrospectively. The suitability of each procedure as a sampling technique for CGP and, in the cases actually analyzed, the distribution of the detected gene aberration were assessed. In total, 122 patients were eligible for analysis; the median age was 61 (range, 29-86) years, and 71 (58.2%) patients were male. Primary intrathoracic tumors were found in 91 (74.6%) cases, including 84 (68.9%) primary lung cancers; the remaining thoracic metastases of extrathoracic origin included various types. The suitability rates of specimens obtained using conventional bronchoscopy with and without cryobiopsy, endobronchial ultrasound-guided transbronchial needle aspiration, and medical thoracoscopy were 82.8% (24/29), 70.4% (19/27), 72.9% (35/48), and 100% (18/18), respectively. Of the 96 cases judged suitable, 83 were subjected to CGP, and all but one were successfully analyzed. Finally, 47 (56.6%) patients had at least one actionable gene aberration and eight (9.6%) were treated with the corresponding targeted therapies. In conclusion, specimens obtained through respiratory endoscopy are suitable for CGP; medical thoracoscopy and cryobiopsy in conventional bronchoscopy are particularly useful.

Tumor microenvironment-mediated immune profiles and efficacy of anti-PD-L1 antibody plus chemotherapy stratified by DLL3 expression in small-cell lung cancer.

BACKGROUND: Delta-like ligand 3 (DLL3) is a therapeutic target in small-cell lung cancer (SCLC). However, how DLL3 expression status affects the tumor microenvironment (TME) and clinical outcomes in SCLC remains unclear. METHODS: This retrospective study included patients with postoperative limited-stage (LS)-SCLC and extensive-stage (ES)-SCLC treated with platinum and etoposide (PE) plus anti-programmed cell death ligand 1 (PD-L1) antibody. We investigated the relationship of DLL3 expression with TME, mutation status, tumor neoantigens, and immunochemotherapy. RESULTS: In the LS-SCLC cohort (n = 59), whole-exome sequencing revealed that DLL3High cases had significantly more neoantigens (P = 0.004) and a significantly higher rate of the signature SBS4 associated with smoking (P = 0.02) than DLL3Low cases. Transcriptome analysis in the LS-SCLC cohort revealed that DLL3High cases had significantly suppressed immune-related pathways and dendritic cell (DC) function. SCLC with DLL3High had significantly lower proportions of T cells, macrophages, and DCs than those with DLL3Low. In the ES-SCLC cohort (n = 30), the progression-free survival associated with PE plus anti-PD-L1 antibody was significantly worse in DLL3High cases than in DLL3Low cases (4.7 vs. 7.4 months, P = 0.01). CONCLUSIONS: Although SCLC with DLL3High had a higher neoantigen load, these tumors were resistant to immunochemotherapy due to suppressed tumor immunity by inhibiting antigen-presenting functions.

Utility of the endobronchial Watanabe spigot for intractable cancer-related pneumothorax: a retrospective observational study.

BACKGROUND: The use of endobronchial Watanabe spigots for intractable secondary pneumothorax in patients with cancer has not been adequate. This study aimed to investigate the use of endobronchial Watanabe spigots for intractable pneumothorax in patients with malignant tumors. METHODS: Consecutive patients with malignant tumors who underwent occlusion with an endobronchial Watanabe spigot for intractable pneumothorax associated with perioperative treatment or drug therapy at our institution between January 2014 and February 2022 were reviewed. RESULTS: Of the 32 cases in which an endobronchial Watanabe spigot was used, six were excluded; we thus evaluated 26 cases in which the chest tube was removed. Chest tubes were removed in 19 cases (73.1%) and could not be removed and required surgical treatment under general anesthesia in seven patients (26.9%), of which four (14.8%) underwent open-window thoracostomy. Half of the patients were treated with both an endobronchial Watanabe spigot and pleurodesis. Although thin-slice chest computed tomography revealed a fistula in 15 patients, the chest tube was removed in 11 (57.9%) patients. A significant difference was only observed in patients with a history of heavy smoking. CONCLUSIONS: The chest tube removal rate was comparable to those reported in previous studies. An endobronchial Watanabe spigot may be a useful treatment option for intractable cancer-related pneumothorax.

Feasibility of Modified Endobronchial Ultrasound-Guided Intranodal Forceps Biopsy: A Retrospective Analysis.

BACKGROUND: Endobronchial ultrasound (EBUS)-guided intranodal forceps biopsy (IFB), a diagnostic bronchoscopic technique for intrathoracic lymphadenopathy, is performed following EBUS-guided transbronchial needle aspiration (TBNA). The current EBUS-IFB technique is complex and provides small sample volumes. We modified this technique to allow the use of standard-sized forceps. OBJECTIVES: The aim of this study was to assess the feasibility of the modified EBUS-IFB technique, which combines standard-sized forceps with standard EBUS-TBNA equipment. METHOD: This retrospective analysis included consecutive patients scheduled for EBUS-TBNA with attempted additional IFB between July 2020 and March 2021. The feasibility indices of IFB, technical success rate, diagnostic accuracy, and major complications were retrospectively investigated. We performed semi-quantitative evaluation of the histological specimens and univariable analyses to identify factors associated with IFB failure. RESULTS: During the study period, 295 patients underwent 307 EBUS-TBNAs; 195 cases were included in the analyses. Target lesions were mainly mediastinal lymph nodes (134 cases, 68.7%); the most frequent sites were #7 (61 cases) and #4R (50 cases). The median lesion size was 16.1 mm, the technical IFB success rate was 90.8%, and the diagnostic accuracy of the TBNA and IFB combination was 99.5%. One patient was lost to follow-up. Univariable analyses did not identify any factors involved in technical IFB failure. Major complications of pneumonia and pneumothorax occurred in 2 cases (1.0%). The median histological score was significantly higher in the IFB group than in the TBNA group (1.67 vs. 1.50, p = 0.032). CONCLUSIONS: Modified EBUS-IFB, combining standard-sized forceps with common EBUS-TBNA equipment, is feasible with few major complications.

A Diagnostic Predictive Model of Bronchoscopy with Radial Endobronchial Ultrasound for Peripheral Pulmonary Lesions.

BACKGROUND: Several factors have been reported to affect the diagnostic yield of bronchoscopy with radial endobronchial ultrasound (R-EBUS) for peripheral pulmonary lesions (PPLs). However, it is difficult to accurately predict the diagnostic potential of bronchoscopy for each PPL in advance. OBJECTIVES: Our objective was to establish a predictive model to evaluate the diagnostic yield before the procedure. METHOD: We retrospectively analysed consecutive patients who underwent diagnostic bronchoscopy with R-EBUS between April 2012 and October 2015. We assessed the factors that were predictive of successful bronchoscopic diagnosis of PPLs with R-EBUS using a multivariable logistic regression model. The accuracy of the predictive model was evaluated using the receiver operator characteristic area under the curve (ROC AUC). Internal validation was analysed using 10-fold stratified cross-validation. RESULTS: We analysed a total of 1,634 lesions; the median lesion size was 25.0 mm. Of these, 1,138 lesions (69.6%) were successfully diagnosed. In the predictive logistic model, significant factors affecting the diagnostic yield were lesion size, lesion structure, bronchus sign, and visible on chest X-ray. The predictive model consisted of seven factors: lesion size, lesion lobe, lesion location from the hilum, lesion structure, bronchus sign, visibility on chest X-ray, and background lung. The ROC AUC of the predictive model was 0.742 (95% confidence interval: 0.715-0.769). Internal validation using 10-fold stratified cross-validation revealed a mean ROC AUC of 0.734. CONCLUSIONS: The predictive model using the seven factors revealed a good performance in estimating the diagnostic yield.

Diagnostic value of a new cryoprobe for peripheral pulmonary lesions: a prospective study.

BACKGROUND: Cryobiopsy is an established technique that yields larger and higher-quality samples than does a forceps biopsy. However, it remains underutilised in the diagnosis of peripheral pulmonary lesions (PPLs), mainly because of difficulties in handling conventional cryoprobes. A recently introduced single-use cryoprobe with a smaller diameter and more flexibility than conventional ones may improve its diagnostic ability for PPLs. We conducted this prospective study to evaluate the feasibility of transbronchial cryobiopsy in the diagnoses of PPLs, using a new 1.7-mm cryoprobe. METHODS: The study included patients with PPLs less than 30 mm in diameter scheduled to undergo bronchoscopy. All the procedures were performed using a combination of virtual bronchoscopic navigation, radial endobronchial ultrasound (R-EBUS) and X-ray fluoroscopy, and all the samples were collected using the cryoprobe alone. Thereafter, we assessed the diagnostic outcomes and safety profiles. RESULTS: A total of 50 patients were enrolled and underwent cryobiopsy. The median lesion size was 20.8 mm (range, 8.2-29.6 mm), and the negative bronchus sign was seen in 34% of lesions. The diagnostic yield was 94% (95% confidence interval, 83.5-98.8%). A positive bronchus sign had a significantly higher diagnostic yield than did a negative bronchus sign (100% vs. 82.4%; P = 0.035). The yield was achieved regardless of other variables, including lesion size, location, and R-EBUS findings. The major complications were mild and moderate bleeding in 28% and 62% of patients, respectively. Pneumothorax was identified in one patient. CONCLUSION: Transbronchial cryobiopsy using the new 1.7-mm cryoprobe is a feasible procedure that has the potential to increase the diagnostic accuracy for PPLs. TRIAL REGISTRATION: Japan Registry of Clinical Trials, jRCT1032200065. Registered July 8 2020, https://jrct.niph.go.jp/en-latest-detail/jRCT1032200065.

Feasibility of next-generation sequencing (Oncomine™ DX Target Test) for the screening of oncogenic mutations in advanced non-small-cell lung cancer patients.

BACKGROUND: The Oncomine™ Dx Target Test based on next-generation sequencing has been approved for the screening of oncogenic mutations in advanced non-small-cell lung cancer patients. METHODS: We assessed the tissue sample factors that affect the success rate of Oncomine™ Dx Target Test companion diagnostics and the feasibility of using biopsy specimens for Oncomine™ Dx Target Test companion diagnostics in advanced non-small-cell lung cancer patients. RESULTS: Ninety-nine biopsy samples were subjected to genetic testing using the Oncomine™ Dx Target Test companion diagnostics to detect v-raf murine sarcoma viral oncogene homologue B1 mutations (Cohort 1), and 136 biopsy samples were examined using Oncomine™ Dx Target Test companion diagnostics for the detection of multiple oncogenic mutations (Cohort 2) between July 2018 and April 2020. We retrospectively collected clinical and pathological data, including tissue size and tumour cell content. The success rate was 77% (76/99) in Cohort 1 and 93% (127/136) in Cohort 2. In Cohort 1, the success rate was significantly associated with the tumour cell content: the success rate was 63% for samples with a tumour cell content of <20%, whereas it was 83% for samples with a tumour cell content of 20% or higher (P = 0.0446). The tissue size also affected the success rate: a success rate of 57% was obtained for tissue sizes <4 mm2, whereas a success rate of 95% was obtained for tissue sizes of 4 mm2 or larger (P < 0.0001). In Cohort 2, the success rate was 100% when tumour specimens with a tissue size of 4 mm2 or larger were used. CONCLUSIONS: Tissue size and tumour cell content were significantly associated with the success rate of Oncomine™ Dx Target Test companion diagnostics.

The utility of transbronchial rebiopsy for peripheral pulmonary lesions in patients with advanced non-squamous non-small cell lung cancer.

BACKGROUND: Patients treated for non-squamous (non-Sq) non-small cell lung cancer (NSCLC) often require repeat biopsies to determine the optimal subsequent treatment. However, the differences between rebiopsy and initial biopsy in terms of their diagnostic yields and their ability to test the molecular profiles using bronchoscopy with radial endobronchial ultrasound guidance in patients with advanced NSCLC remain unclear. Hence, we aimed to compare the diagnostic yields and ability for molecular analyses of rebiopsies with those of initial biopsies. METHODS: We investigated 301 patients with advanced non-Sq NSCLC who underwent radial endobronchial ultrasound-guided transbronchial biopsy (TBB) for peripheral pulmonary lesions (PPLs) between August 2014 and July 2017. Patients were divided into the rebiopsy and initial biopsy groups: the latter referred to the biopsy that determined the definitive diagnosis. The diagnostic yields and ability for molecular analyses were compared between the two groups, and the factors affecting the TBB diagnostic yield were identified using univariate and multivariate analyses. RESULTS: The diagnostic yields of the rebiopsy and initial biopsy groups were comparable (86.8 and 90.8%, respectively; p = 0.287). Furthermore, 93.0 and 94.0% of the patients in the rebiopsy and initial biopsy groups, respectively, had adequate specimens for gene profiling and mutational analysis (p = 0.765). The factors that increased the diagnostic yield were a positive bronchus sign (p < 0.001) and tumour location within the internal two-thirds of the lungs (p = 0.026). CONCLUSIONS: The PPL diagnostic yield of the rebiopsy group was as high as that of the initial biopsy group. Hence, TBB for PPLs is feasible for patients requiring rebiopsy as well as for those with initial diagnoses. Adequate, high-quality biopsy specimens can be obtained by transbronchial rebiopsy for molecular testing.

Cryobiopsy during flex-rigid pleuroscopy: an emerging alternative biopsy method in malignant pleural mesothelioma. A comparative study of pathology.

BACKGROUND: Malignant pleural mesothelioma (MPM) is rarely an asbestos-related cancer with a poor prognosis that is difficult to distinguish from some benign conditions by using conventional biopsy techniques. The purpose of this study was to evaluate the utility of a novel biopsy technique using a cryoprobe during flex-rigid pleuroscopy for diagnosing MPM. METHODS: Consecutive patients who underwent pleural cryobiopsy during flex-rigid pleuroscopy from June through November 2017 to diagnose the cause of pleural effusion were collected. From these, cases ultimately diagnosed as MPM were selected. Pleural biopsies were performed by using conventional instruments followed by a cryoprobe. The obtained samples were histologically examined and compared with regard to the quality (sample size, tissue depth, and crush rate), immunohistochemical (IHC) staining, and p16 by fluorescence in situ hybridization (FISH). RESULTS: In total, five patients ultimately diagnosed as MPM were enrolled. The sample collected was significantly larger for cryobiopsy than conventional biopsy (18.9 mm2 vs. 6.7 mm2, P < 0.001). Full-thickness biopsies were achieved in four cases by using cryobiopsy compared with one case by conventional biopsy. Moreover, the crush rate was significantly less for cryobiopsy than conventional biopsy (9% vs. 35%, P < 0.001). The results of IHC staining and p16 by FISH were similar between biopsy techniques. Cryobiopsy successfully led to accurate diagnosis of MPM in all cases, whereas conventional biopsy was diagnostic in one case. No severe complications developed after either biopsy technique. CONCLUSION: Cryobiopsy during flex-rigid pleuroscopy is a feasible and convenient biopsy technique that supports precise diagnosis of MPM.

Utility of rapid on-site cytologic evaluation during endobronchial ultrasound with a guide sheath for peripheral pulmonary lesions.

OBJECTIVE: The utility of rapid on-site evaluation during endobronchial ultrasound with a guide sheath for peripheral pulmonary lesions is unclear. The aim of this study was to evaluate the role of rapid on-site evaluation during endobronchial ultrasound with a guide sheath for peripheral pulmonary lesions. METHODS: Consecutive patients who underwent endobronchial ultrasound with a guide sheath for the diagnosis of peripheral pulmonary lesions at our hospital between September 2012 and July 2014 were included in this retrospective study. Cytology slides were air-dried, and modified Giemsa (Diff-Quik) staining was used for rapid on-site evaluation. Additional smears were prepared for Papanicolaou staining and tissue samples were placed in formalin for histologic evaluation. The results of rapid on-site evaluation were compared with the final diagnoses of endobronchial ultrasound with a guide sheath. RESULTS: A total of 718 cases were included in the study population. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of rapid on-site evaluation during endobronchial ultrasound with a guide sheath for peripheral pulmonary lesions was 88.6%, 65.9%, 81.2%, 77.7% and 80.1%, respectively. There were no procedure-related deaths. CONCLUSIONS: Rapid on-site evaluation during endobronchial ultrasound with a guide sheath had high sensitivity for peripheral pulmonary lesions. When carrying out rapid on-site evaluation of transbronchial biopsy samples from peripheral pulmonary lesions, careful interpretation and clinical correlation are necessary.

Bronchoscopic Re-biopsy for Mutational Analysis of Non-small Cell Lung Cancer.

OBJECTIVES: Currently, several acquired resistance mechanisms and rare driver oncogenes are identified in non-small cell lung cancer (NSCLC) relapses. Re-biopsy increases valuable information to guide treatment strategies, but the utility and feasibility of bronchoscopic re-biopsy has not been investigated. METHODS: We studied 70 patients who underwent bronchoscopic for re-biopsy of NSCLC that was resistant to at least one regimen of chemotherapy or molecular-targeted therapy between January 2013 and December 2014. We assessed clinical data, technical success rate, and mutational analysis. RESULTS: Procedures performed were transbronchial biopsy (n = 52) and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) (n = 18). Overall detection rate of re-biopsy for malignant cells was 87 % (83 % for TBB and 100 % for EBUS-TBNA). Mutational analysis was possible in almost all technically successful cases; likewise, acquired-resistant mutations (55 % of EGFR mutants) and small cell lung cancer transformation were identified from the bronchoscopy specimens. Other driver mutations were seen in four cases, including ALK fusion gene (n = 2) and ROS1 fusion gene (n = 2). There were no associated severe complications. CONCLUSION: This study shows that bronchoscopic re-biopsy for NSCLC is feasible and provides adequate samples that enable identification of resistance mutations and rare driver oncogenes.

Re-biopsy by endobronchial ultrasound procedures for mutation analysis of non-small cell lung cancer after EGFR tyrosine kinase inhibitor treatment.

BACKGROUND: Re-biopsy for resistant non-small cell lung cancer (NSCLC) after treatment with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is important for selection of better therapy, but there have been no reports about the utility of endobronchial ultrasound (EBUS)-guided procedures for such purpose. The aim of this study was to evaluate the utility of EBUS-guided re-biopsy for resistant NSCLC after treatment with EGFR-TKIs. METHODS: From January 2013 to December 2015, 53 consecutive patients who underwent EBUS-guided re-biopsy for mutation analysis of NSCLC after EGFR-TKI treatment were assessed. RESULTS: Nine patients underwent EBUS-guided transbronchial needle aspiration (EBUS-TBNA) and 44 patients underwent EBUS with a guide sheath (EBUS-GS) transbronchial biopsy. The technical success rates were 100 %. As for mutation analysis, all 9 specimens (100 %) from EBUS-TBNA and 33 specimens (75.0 %) from EBUS-GS were adequate for gene profiling. The remaining 11 specimens from EBUS-GS procedures were inadequate for mutation analysis owing to the absence of tumor component in the sample (n = 6) or insufficient specimen (n = 5). There were no related severe complications. CONCLUSIONS: Re-biopsy by both EBUS-TBNA and EBUS-GS were useful and safe sampling procedures for mutation analysis of EGFR-TKI resistant NSCLC.

Solitary Pure Ground-Glass Nodules 5 mm or Smaller: Frequency of Growth.

PURPOSE: To clarify the percentage of solitary pure ground-glass nodules (SPGGNs) 5 mm or smaller that grow and develop into invasive adenocarcinomas. MATERIALS AND METHODS: This study was approved by the institutional review board, and informed consent was obtained from all people who were screened. From February 2004 through December 2007, 7294 participants underwent screening for lung cancer with computed tomographic (CT) imaging. The nodule database was reviewed to identify SPGGNs 5 mm or smaller. Growth of the SPGGNs was evaluated as of March 31, 2013. In cases of pathologic analysis-proven adenocarcinomas that developed from SPGGNs 5 mm or smaller, solid components were evaluated. Percentages, 95% confidence intervals, and means were calculated. RESULTS: At baseline screening, 438 SPGGNs 5 mm or smaller were identified, and during the study period one SPGGN 5 mm or smaller developed de novo. Of the 439 SPGGNs, 394 were stable and 45 (10.3% [95% confidence interval: 7.5%, 13.7%]), including newly developed SPGGN, grew. Of the 45 SPGGNs that grew, 0.9% (four of 439 [95% confidence interval: 0.3%, 2.3%]) developed into adenocarcinomas (two minimally invasive [including the newly developed SPGGN] and two invasive). The mean period between baseline CT screening and the appearance of solid components in the four adenocarcinomas was 3.6 years. CONCLUSION: Of SPGGNs 5 mm or smaller, approximately 10% will grow and 1% will develop into invasive adenocarcinomas or minimally invasive adenocarcinomas. SPGGNs 5 mm or smaller should be rescanned 3.5 years later to look for development of a solid component.

Radial endobronchial ultrasound images for ground-glass opacity pulmonary lesions.

Radial endobronchial ultrasound (R-EBUS) is a useful tool for precise localisation of peripheral pulmonary lesions, but there have been no detailed reports about the use of R-EBUS images for ground-glass opacity (GGO). The R-EBUS images of 116 patients with GGO, who were diagnosed as having adenocarcinoma by R-EBUS with a guide sheath (EBUS-GS), were compared with the respective chest computed tomography findings. In 103 patients, R-EBUS images were correlated with the histological surgical specimens. R-EBUS images of GGO were identified based on the internal structure of the lesion and classified into two groups. Blizzard showed an enlarged, diffuse hyperintense acoustic shadow. Mixed blizzard showed a combination of blizzard and some diffuse heterogeneity with several hyperechoic dots and vessels. All pure GGO lesions (nine out of nine) were blizzard on R-EBUS. For part-solid GGOs, the percentage of mixed blizzard was inversely related to the amount of the GGO component. Histological findings from surgery revealed that all blizzard lesions were on the spectrum of adenocarcinoma in situ to well differentiated adenocarcinoma while majority (33 out of 64) of mixed blizzard lesions were moderately to poorly differentiated adenocarcinoma. R-EBUS types are important to locate GGOs prior to transbronchial sampling with EBUS-GS.

Novel use for an EGFR mutation-specific antibody in discriminating lung adenocarcinoma from reactive pneumocyte hyperplasia.

AIMS: Pulmonary ground-glass nodules (GGNs) are frequently observed. Histopathologically, their presentation can indicate a wide range of disorders from an inflammatory process to malignancy. An accurate diagnosis based on GGNs can sometimes be challenging on small-sized biopsies. Mutations in the EGFR gene are detected in pulmonary adenocarcinomas (ADCs). Immunohistochemical analysis using antibodies that detect specific EGFR mutations has been shown to correlate with mutational status as determined by molecular methods. We hypothesized that these antibodies could be used to discriminate between ADCs and benign pneumocyte hyperplasias. METHODS AND RESULTS: Surgically resected, pre-invasive to invasive lung ADC (n = 32) and reactive pneumocyte hyperplasia (n = 40) tissue samples were probed with antibodies against EGFR mutations, p53, Mouse double minute 2 and 14-3-3 sigma. Of the 32 lung ADC specimens analysed, 12 (38%) were positive using the EGFR mutation-specific antibodies, while no immunoreactivity was observed in reactive pneumocyte hyperplasia specimens. Analyses of receiver operating characteristic curves showed that the highest area under the curve values were associated with the use of EGFR mutation-specific antibodies. In addition, a high concordance rate was observed between surgically resected and corresponding biopsy materials using these antibodies. CONCLUSIONS: EGFR mutation-specific antibodies can be used to discriminate between lung ADC and benign pneumocyte hyperplasia, even in small-sized biopsies.

The diagnostic value of histology and cytology samples during endobronchial ultrasound with a guide sheath.

OBJECTIVE: Endobronchial ultrasound with a guide sheath has been a widely used diagnostic procedure for peripheral pulmonary lesions. After sequential sampling with the usual devices, small portions of the collected specimen remain in the guide sheath and these can potentially contribute to diagnosis. We assessed the diagnostic value of each histological and cytological sample, especially the guide sheath flush, for pulmonary malignancies. METHODS: The medical records of patients who were diagnosed to have peripheral lung cancer by endobronchial ultrasound with a guide sheath in our hospital between January 2014 and May 2014 were reviewed. Separate samples from forceps biopsy, bronchial brushing, device wash, guide sheath flush and bronchial lavage were compared and analyzed. RESULTS: A total of 106 consecutive patients (54 men, 52 women, median age 69.0 years) were included. The median long axis size of the lesions was 26.0 mm. A definitive diagnosis was made in 90.6% of forceps biopsy samples and in 85.8% of all cytology samples combined. Individual yields were 61.3% from brushing, 77.4% from device wash, 72.6% from guide sheath flush and 32.1% from bronchial lavage. The diagnosis yield from forceps biopsy was significantly higher than each cytological sampling method (P < 0.05). Among the cytological sampling methods, yield from bronchial lavage was significantly the lowest (P < 0.001). CONCLUSIONS: Forceps biopsy is an important sampling method during endobronchial ultrasound with a guide sheath for peripheral pulmonary lesions. In the collection of diagnostic liquid samples, guide sheath flush is more advantageous than bronchial lavage and provides specimen that may be adequate for molecular testing.