Transbronchial Biopsy Specimens Research Articles

Expression of Nedd9 in Transbronchial Biopsies of Lung Adenocarcinoma.

SUMMARY – Lung cancer as the major cause of cancer mortality worldwide includes several histologic subtypes evolving from numerous genetic and epigenetic changes emerging in alveolar, bronchiolar and bronchial epithelium. The majority of cases are diagnosed in advanced stage (i.e. stages IIIB and IV), often with scanty amount of tissue in transbronchial biopsies or cytology specimens. The aim of the present study was to investigate the expression of the scaffolding protein neural precursor cell expressed, developmentally downregulated 9 (NEDD9) in small biopsies of lung adenocarcinoma. The expression of NEDD9 was analyzed immunohistochemically in 71 formalin-fixed and paraffin-embedded transbronchial biopsy specimens of primary lung adenocarcinoma. Nuclear and cytoplasmic NEDD9 expression was detected indicating activation of the epithelial-mesenchymal transition process. Direct relationship between the expression of NEDD9 and survival was not demonstrated.

UTILITY OF PROBE‐BASED CONFOCAL LASER ENDOMICROSCOPY FOR RAPID EVALUATION IN TRANSBRONCHIAL BIOPSY SPECIMENS

RespirologyVolume 22, Issue S3 p. 27-27 Bronchoscopy and Interventional Techniques UTILITY OF PROBE-BASED CONFOCAL LASER ENDOMICROSCOPY FOR RAPID EVALUATION IN TRANSBRONCHIAL BIOPSY SPECIMENS First published: 23 November 2017 https://doi.org/10.1111/resp.13206_59Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume22, IssueS3Supplement: 22nd Congress of the Asian Pacific Society of Respirology, International Convention Centre, Sydney, Australia, 23–26 November 2017November 2017Pages 27-27 RelatedInformation

Miliary Tuberculosis that Developed after Intravesical Bacillus Calmette-Guerin Therapy.

As a treatment for superficial transitional cell carcinoma, Bacillus Calmette-Guerin (BCG) intravesical instillation can rarely cause unpredictable systemic side effects. We describe a patient admitted due to continuous pyrexia and general fatigue. He was previously treated with intravesical BCG. Laboratory data indicated a hepatic disorder, and chest computed tomography revealed extensive bilateral miliary nodules. Transbronchial lung biopsy specimens showed several small noncaseating granulomas. The diagnosis was unsolved on the basis of acid fast staining, polymerase chain reaction and microbiological cultures, so we considered the possibility of BCG side effect-induced granuloma. Two months after treatment with antituberculous agents and corticosteroids, his clinical symptoms were improved.

A case of wild-type transthyretin amyloidosis associated with organizing pneumonia.

An 81-year-old man was referred to our hospital with bilateral multiple patchy opacities on chest radiography. His chief complaints were a few months’ history of intermittent mild cough and slightly yellow sputum. Chest computed tomography (CT) showed non-segmental air-space consolidations with ground-glass opacities. Amyloid deposition with organizing pneumonia (OP) was seen in transbronchial lung biopsy (TBLB) specimens from the left S8. Three months later, the infiltration originally seen in the left lower lobe was remarkably diminished, and new infiltrations in the lingual and right lower lobes were detected on chest CT. Amyloid deposition with OP was seen in TBLB specimens from the left S4. Transthyretin was detected following immunohistochemical examination. The presence of wild-type transthyretin (ATTRwt) was proven using genetic analysis. The present report describes a rare case of ATTRwt amyloidosis associated with OP.

Comparison of Clinically Relevant Mutation Profiles Between Preoperative Biopsy and Corresponding Surgically Resected Specimens in Japanese Patients With Non–Small-cell Lung Cancer by Amplicon-based Massively Parallel Sequencing

BackgroundAmplicon-based massively parallel sequencing (MPS) is an effective platform for identifying clinically actionable mutations across many genes in limited amounts of tissue. Most lung cancers are diagnosed and staged using small tissue samples obtained by transbronchial biopsy (TBB). To determine whether the mutations in TBB specimens detected by amplicon-based MPS reflect those present in the tumors, we compared the mutational profiles of preoperative TBB specimens and corresponding surgically resected specimens. Patients and MethodsFresh-frozen primary tumor specimens from non–small-cell lung cancer patients (n = 46) obtained preoperatively by TBB and during surgical resection were analyzed. The concordance of mutations detected by amplicon-based MPS in the 2 sample types was investigated, and the allele frequency of the mutations common to both specimens from the same patient was determined. ResultsAn initial assessment of DNA quantity revealed that 46% of the TBB specimens (21 of 46) had less than the lower limit for amplicon-based MPS. These 21 TBB specimens were consequently omitted from the analysis. Of the 29 mutations detected in the TBB and/or surgically resected specimens from 25 patients, 23 were present in both samples, for a concordance rate of 79%. ConclusionAmplicon-based MPS with TBB specimens approximately reflects clinically relevant tumor mutation profiles. However, the rate of TBB specimens with sufficient DNA quantity for amplicon-based MPS was only around 50%. Therefore, surgically resected specimens have a valuable role in exploratory and comprehensive genomic profiling.

SPARC is a possible predictive marker for albumin-bound paclitaxel in non-small-cell lung cancer.

ObjectivesNanoparticle albumin-bound paclitaxel (nab-paclitaxel) produced good tumor response in cases with lung squamous cell carcinoma, one of the most difficult cancers to treat. Secreted protein acidic and rich in cysteine (SPARC) binds to albumin, suggesting that SPARC plays an important role in tumor uptake of nab-paclitaxel. There is as yet no predictive marker for cytotoxic agents against non-small-cell lung cancer (NSCLC), and hence we believed that SPARC expression might be associated with tumor response to nab-paclitaxel.Patients and methodsWe studied stromal SPARC reactivity and its association with clinicopathological characteristics in 200 cases of NSCLC using a custom tissue microarray fabricated in our laboratory by immunohistochemical staining. We also investigated the relationship between stromal SPARC reactivity and tumor response to nab-paclitaxel using biopsy or surgical specimens obtained from advanced or recurrent lung cancer patients.ResultsHigh SPARC stromal reactivity (>50% of optical fields examined) was detected in 16.5% of cases and intermediate SPARC reactivity (10%–50%) in 56% of cases. High expression in cancer cells was rare (five cases). Stromal SPARC level was correlated with smoking index, squamous cell carcinoma, and vessel invasion. Furthermore, patients with high stromal SPARC reactivity in biopsy specimens such as transbronchial lung biopsy or surgical specimens tended to respond better to nab-paclitaxel.ConclusionStromal SPARC was detected by immunohistochemical staining in ∼70% of NSCLC cases, and good tumor response to nab-paclitaxel was correlated with high stromal SPARC reactivity. SPARC may be a useful predictive marker for selecting patients likely to respond favorably to nab-paclitaxel treatment.

Toxoplasma gondii pseudocyst in a transbronchial biopsy: a case report.

BackgroundWe herein present a case in which a Toxoplasma cyst was found in a transbronchial biopsy specimen from an immunocompetent patient with negative serology for the parasite.Case presentationAn 18-year-old Brazilian man presented with a 1-week history of dyspnea and fever and was diagnosed with right lower lobe pneumonia. He began inpatient treatment with intravenous antibiotics. During treatment, a bronchoscopy with bronchoalveolar lavage and transbronchial biopsy was performed. Anatomopathological examination of the transbronchial biopsy showed a small fragment of lung parenchyma with discrete septal thickening and a rounded structure, suggestive of a pseudocyst containing Toxoplasma gondii bradyzoites. However, serological tests were negative for immunoglobulin G and immunoglobulin M.ConclusionsBronchoscopy is a minimally invasive, effective diagnostic and therapeutic method. Despite the fact that the Toxoplasma pseudocyst in the present case was not the cause of the patient’s comorbidities, bronchoscopy with transbronchial biopsy allowed for an incidental diagnosis of a Toxoplasma pseudocyst with minimal invasiveness.

Osimertinib-induced interstitial lung disease after treatment with anti-PD1 antibody

SummaryWe report a case of a 38-year-old woman who was diagnosed with stage IV lung adenocarcinoma, harboring an epidermal growth factor receptor (EGFR) L858R mutation on exon 21 and a T790 M mutation on exon 20. The patient was treated with osimertinib, a third-generation EGFR tyrosine kinase inhibitor (EGFR-TKI) following treatment with nivolumab, an anti-Programmed Cell Death 1 (anti-PD1) antibody. After initiating osimertinib treatment, the patient began to complain of low-grade fever and shortness of breath without hypoxemia, and her chest radiograph and a CT scan revealed a remarkable antitumor response, although faint infiltrations were observed in the bilateral lung field. Bronchoalveolar lavage fluid mainly contained lymphocytes (CD4+/CD8+ ratio of 0.3), and a transbronchial lung biopsy specimen showed lymphocytic alveolitis with partial organization in several alveolar spaces. Therefore we diagnosed the patient with osimertinib-induced interstitial lung disease (ILD) after treatment with anti-PD1 antibody. We considered anti-PD1 therapies may be the risk factor of EGFR-TKI-induced ILD.

Mast cell phenotypes in the allograft after lung transplantation.

The burden of mast cell (MC) infiltration and their phenotypes, MC-tryptase (MCT ) and MC-tryptase/chymase (MCTC ), after lung transplantation (LT) has not been evaluated in human studies. We reviewed 20 transbronchial lung biopsy (TBLB) specimen from patients with early normal allograft (<6months post-LT, n=5), late normal allograft (>6months, n=5), A2 or worse acute cellular rejection (ACR, n=5), and chronic lung allograft dysfunction (CLAD, n=5). Slides were immunostained for tryptase and chymase. Total MC, MCT , MCTC and MCTC to-MCT ratio were compared between the four groups using a generalized linear mixed model. Irrespective of clinicopathologic diagnosis, MC burden tends to increase with time (r(2) =.56, P=.009). MCTC phenotype was significantly increased in the CLAD group (8.2±4.9 cells per HPF) in comparison with the other three groups (early normal: 1.6±1.7, P=.0026; late normal: 2.5±2.3, P=.048; ACR: 2.7±3.5, P=.021). Further, the ratio of MCTC to MCT was significantly increased in CLAD group as compared to the other three groups (P<.001 for all comparisons). The burden of MC may increase in the allograft as function of time. Patients with CLAD have an increased relative and absolute burden of MCTC phenotype MC. Future studies are needed to confirm these findings and evaluate the potential pathologic role of MCTC in allograft dysfunction.

Dipeptidyl peptidase-4 is highly expressed in bronchial epithelial cells of untreated asthma and it increases cell proliferation along with fibronectin production in airway constitutive cells.

BackgroundType 2 helper T-cell cytokines including IL-13 play a central role in the pathogenesis of bronchial asthma (BA). During the course of our research, our attention was drawn to dipeptidyl peptidase-4 (DPP4) as one of the molecules that were induced from bronchial epithelial cells (BECs) by IL-13 stimulation. DPP4 could become a new biomarker or therapeutic target. The aim of this study was to investigate the expression of DPP4 in the asthmatic airway, and its role in the pathophysiology of asthma.MethodsBECs were isolated from patients with inhaled corticosteroid-treated asthma (stBA) and inhaled corticosteroid-naïve asthma (snBA) using bronchoscopy.DPP4 mRNA expression in freshly isolated BECs and primary cultured BECs with or without IL-13 stimulation was investigated by microarray analysis and quantitative real-time PCR (qPCR). The distribution of DPP4 protein was determined by immunostaining of transbronchial lung biopsy specimens from asthma patients. The effect of recombinant human (rh) DPP4 on the proliferation of lung fibroblasts (HFL-1) and bronchial smooth muscle cells (BSMCs) was examined, as well as its effect on the production of fibronectin (FN).ResultsDPP4 mRNA was strongly expressed in freshly isolated BECs in snBA, and its expression was significantly enhanced by IL-13 stimulation. DPP4 mRNA expression in BECs of snBA significantly correlated with exhaled nitric oxide. Biopsied tissues of the asthmatic airway revealed strong expression of DPP4 protein in BECs from snBA subjects. rhDPP4 stimulated the proliferation of HFL-1 and BSMCs, and it also enhanced production of FN from these airway cells.ConclusionDPP4 may be involved in the pathologic features of asthmatic airway inflammation and cell proliferation and FN production.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-016-0342-7) contains supplementary material, which is available to authorized users.

Clinical and high-resolution computed tomography characteristics of the welder's pneumoconiosis

To investigate the clinical and high-resolution computed tomography (HRCT) features of the welder's pneumoconiosis. A total of 10 patients diagnosed by bronchoscopy and pathology from January 2010 to January 2015 in Nanjing Drum Tower Hospital were recruited in this study, and the clinical manifestations, pulmonary function tests, pathology and HRCT data were collected and analyzed retrospectively. Ten patients all had welder's occupational history for 5-30 years, with the main clinical manifestations of cough, sputum production, chest tightness and other symptoms. And the ratio of forced expiratory volume in one second and forced vital capacity (FEV1/FVC) of 4 patients was lower than 75.0% in the pulmonary function tests. Transbronchial lung biopsy specimen showed numerous hemosiderin-laden macrophages within the alveolar space, associated with positive iron staining. In welder's pneumoconiosis, small centrilobular nodules (10 cases) were frequently seen on HRCT in bilateral lung fields, with branching linear structures or the tree buds like shadows in 7 cases; 3 patients also showed areas of ground-glass attenuation. And the patients were misdiagnosed as tuberculosis (1/10), interstitial pneumonia (3/10), allergic alveolitis (1/10), diffuse lung disease (2/10), and vasculitis (1/10). Clinical manifestations of welder's pneumoconiosis are not specific; small centrilobular nodules are frequently seen on HRCT, with linear opacities or tree bud-like shadows.

Molecular Profiling in Lung Biopsies of Human Pulmonary Allografts to Predict Chronic Lung Allograft Dysfunction

Chronic lung allograft dysfunction (CLAD) is the main reason for poor long-term outcome of lung transplantation, with bronchiolitis obliterans (BO) representing the predominant pathological feature. BO is defined as a progressive fibrous obliteration of the small airways, thought to be triggered by a combination of nonimmune bronchial injury and alloimmune and autoimmune mechanisms. Because biopsy samples are too insensitive to reliably detect BO and a decline in lung function test results, which is clinically used to define CLAD, does not detect early stages, there is need for alternative biomarkers for early diagnosis. Herein, we analyzed the cellular composition and differential expression of 45 tissue remodeling-associated genes in transbronchial lung biopsy specimens from two cohorts with 18 patients each: patients who did not develop CLAD within 3 years after transplantation (48 biopsy specimens) and patients rapidly developing CLAD within the first 3 postoperative years (57 biopsy specimens). Integrating the mRNA expression levels of the five most significantly dysregulated genes from the transforming growth factor-β axis (BMP4, IL6, MMP1, SMAD1, and THBS1) into a score, patient groups could be confidently separated and the outcome predicted (P < 0.001). We conclude that overexpression of fibrosis-associated genes may be valuable as a tissue-based molecular biomarker to more accurately diagnose or predict the development of CLAD.

Banff study of pathologic changes in lung allograft biopsy specimens with donor-specific antibodies

The diagnosis of antibody-mediated rejection (AMR) in the lung transplant is still an area under investigation. We performed a blinded multicenter study to determine if any statistically significant histologic findings in transbronchial biopsy specimens from lung transplant patients correlate with the presence of donor-specific antibodies (DSAs). We asked 9 pathologists with experience in lung transplantation to evaluate 161 lung transplant biopsy specimens for various histologic parameters. The findings were correlated with antibody status positive for DSAs, positive for non-DSAs, and no antibodies (NABs) present. The significance of each histologic variable was reviewed. We found no statistically significant association with acute cellular rejection, airway inflammation, or bronchiolitis obliterans and the presence or absence of antibodies. However, biopsy specimens with DSAs had a statistically significant difference vs NABs in the setting of acute lung injury, with or without diffuse alveolar damage (p = 0.0008), in the presence of capillary neutrophilic inflammation (p = 0.0014), and in samples with endotheliitis (p = 0.0155). In samples with complement 4d staining, there was a trend but no statistically significant difference between specimens associated with DSAs and specimens with NABs. Capillary inflammation, acute lung injury, and endotheliitis significantly correlated with DSAs. The infrequently observed diffuse staining for complement 4d limits the usefulness of this stain.

Epithelioid pleural mesothelioma concurrently associated with miliary pulmonary metastases and minimal change nephrotic syndrome – A hitherto undescribed case

Malignant pleural mesothelioma (MPM) is the aggressive disease typically spreading along the pleural surface and encasing the lung, leading to respiratory failure or cachexia. Rare cases with atypical clinical manifestation or presentation have been reported in MPM. We experienced a unique case of MPM concurrently associated with miliary pulmonary metastases and nephrotic syndrome. A 73-year-old Japanese man with past history of asbestos exposure was referred to our hospital for the investigation of the left pleural effusion. Chest computed tomography showed thickening of the left parietal pleura. Biopsy specimen of the pleura showed proliferating epithelioid tumor cells, leading to the pathological diagnosis of epithelioid MPM with the aid of immunohistochemistry. After the diagnosis of MPM, chemotherapy was performed without effect. Soon after the clinical diagnosis of progressive disease with skull metastasis, edema and weight gain appeared. Laboratory data met the criteria of nephrotic syndrome, and renal biopsy with electron microscopic examination revealed the minimal change disease. Steroid therapy was started but showed no effect. Around the same time of onset of nephrotic syndrome, multiple miliary lung nodules appeared on chest CT. Transbronchial biopsy specimen of the nodules showed the metastatic MPM in the lung. The patient died because of the worsening of the general condition. To our knowledge, this is the first case of MPM concurrently associated with multiple miliary pulmonary metastases and nephrotic syndrome.

Recurrent Prostate Cancer Presenting as Multiple Lung Metastases with a Low Serum Prostate-specific Antigen Level 5 Years after Prostatectomy: A Case Report

Prostate-specific antigen (PSA) is a glycoprotein produced by prostatic duct and acinar epithelial cells and the most commonly used marker for diagnosing prostate cancer, and for monitoring its progression and recurrence. Here, we describe a 76-year-old patient with recurrent prostate cancer who developed isolated hematogenous pulmonary metastases with a normal serum PSA level 5 years after radical prostatectomy. Immunohistochemical (IHC) analysis of a transbronchial lung biopsy specimen revealed tumor cells positive for PSA and prostatic acid phosphatase. After 2 months of maximal androgen blockade, the metastatic pulmonary nodules showed near-complete regression. In conclusion, metastases of prostate adenocarcinoma may occur despite low serum PSA levels, and, if warranted clinically, IHC staining or other serological markers for prostate adenocarcinoma should be considered when evaluating metastatic carcinoma from an unknown primary lesion in males with low serum PSA levels. (Korean J Med 2015;89:238-242)

Marginal zone B-cell lymphoma of the pulmonary mucosa-associated lymphoid tissue: A case report.

Marginal zone B-cell lymphoma of the pulmonary mucosa-associated lymphoid tissue (pulmonary MALT-MZL) is a common type of primary pulmonary lymphoma, but is rare as a pulmonary malignant tumor. In the present study, a 49-year-old male patient was admitted to The First Affiliated Hospital of Xi'an JiaTong University (Xi'an, China) with a pulmonary lesion in the right upper lung. The patient was diagnosed with pulmonary MALT-MZL subsequent to undergoing chest computed tomography (CT), a routine blood test, pathological and histological examinations, a transbronchial lung biopsy and bronchoscopy. A chest CT scan revealed right middle lobe consolidation and inflammatory signs, accompanied by mediastinal lymphadenopathy in the anterior basal segment of the upper lobe and CT angiogram signs. Bronchial stenosis and swollen mucosa were observed by bronchoscopy. The tissue section of the transbronchial lung biopsy specimens revealed diffusely infiltrated monocytoid B-cell lymphocytes and a lymphoepithelial lesion. The tissue was found to be positive for cluster of differentiation (CD)20, B-cell lymphoma 2 and CD79a expression, but negative for CD3, CD5, cyclin D1 and κ-light chain expression. CD21 and CD23, located in the residual follicular dendritic cells, were detected by immunohistochemical staining. The clinical manifestations of pulmonary MALT-MZL are non-specific and misdiagnosis frequently occurs in clinical practice. Therefore, an appropriate invasive biopsy procedure is necessary for early and accurate diagnosis of pulmonary MALT-MZL. Clinical presentation that includes periodic fever and distended bronchi in pulmonary consolidation may indicate a diagnosis of MALT-MZL. Pulmonary MALT-MZL belongs to the category of indolent lymphoma and accurate clinical diagnosis is challenging. The results in the present study may provide additional evidence for the accurate diagnosis of this rare entity.

An Unusual Cause of Respiratory Failure in a 25-Year-Old Heart and Lung Transplant Recipient

A 25-year-old woman, a never smoker with a history of heart-lung transplantation for World Health Organization group 1 pulmonary arterial hypertension performed 20 months prior to presentation, was evaluated for shortness of breath. Following transplantation, she was initiated on standard therapy of prednisone, tacrolimus, and azathioprine, along with routine antimicrobial prophylaxis. Her posttransplant course was complicated by persistent acute cellular rejection, as determined from a transbronchial biopsy specimen, without evidence of rejection in an endomyocardial biopsy specimen. The immunosuppressive medications were supplemented with pulse-dosed steroids, and the patient was transitioned from azathioprine to mycophenolate mofetil. Sirolimus was added 9 months prior to presentation. Three months prior to presentation, she was admitted for increasing oxygen requirements, shortness of breath, and bilateral infiltrates on the CT scans of the chest.

Clinical significance of intra-alveolar fibrin deposition in transbronchial lung biopsy in patients with organizing pneumonia.

This study examined the clinical significance of intra-alveolar fibrin deposition (IAFD) in transbronchial lung biopsy specimens obtained from patients with organizing pneumonia. Pathological reports of transbronchial lung biopsies performed between 2004 and 2012 were reviewed to identify cases of intra-alveolar organization with or without fibrin deposition. Clinical charts, computed tomography images, and transbronchial lung biopsy specimens from these cases were examined retrospectively. Diagnosis of organizing pneumonia was reevaluated based upon the consensus of a respiratory physician, a radiologist, and a pathologist. Transbronchial lung biopsy results of the reviewed patients with organizing pneumonia found seven patients who had IAFD, and 34 who did not. Seven patients' conditions were associated with collagen vascular disease (CVD), and 34 were cryptogenic. IAFD was significantly associated with high C-reactive protein (CRP) values (>5 mg/dl) (p = 0.0012) and underlying CVD (p = 0.0099). Multivariate analysis revealed that IAFD was independently associated with high CRP values (p = 0.0184). Three of 31 patients and six of 27 patients experienced a relapse of organizing pneumonia within 6 months and 1 year, respectively. IAFD (p = 0.0044) and high CRP values (p = 0.0207) were significantly related to relapse within 6 months, while only CRP was significantly related to relapse within 1 year (p = 0.0007). In patients with organizing pneumonia, IAFD was significantly associated with high CRP values. High CRP values and/or IAFD predicted relapse of organizing pneumonia within 6 months to 1 year.

Comparative assessment of the diagnostic value of transbronchial lung biopsy and bronchoalveolar lavage fluid cytology in lung cancer.

This study was designed to determine the accuracy of bronchoalveolar lavage fluid cytology (BAL) using histopathologic examination of transbronchial biopsy specimens as the gold standard in diagnosis of lung carcinoma at our center. A retrospective study was conducted to investigate a total of 388 patients who were suspected of having lung cancer and had undergone fiberoptic bronchoscopy in Shahid Sadoughi hospital from 2006 to 2011. Lung masses were proven to be malignant by histology. Transbronchial lung biopsy (TBLB) identified malignancy in 183 of the 388 cases, including 48 cases (26.2%) with adenocarcinoma, 4(2.1%) with bronchioloalveolar carcinoma, 47(25.6%)with squamous cell carcinoma, 34(18.5%) with well-diffentiated neuroendocrine carcinoma, 35(19.1%) with small cell carcinoma, 14 (7.6%) with non-small cell carcinoma, and 1 (0.54%) with large cell carcinoma. A total of 205 cases were correctly classified as negative. BAL was also performed in 388 patients; 86/103 cases were consistent with the final diagnosis of lung cancer and 188/285 cases were correctly classified as negative. The sensitivity of BAL was 46.9%(CI:41.9%, 51.8%)) and its specificity was 91.6%(CI:88.8%, 94.3%). BAL had a positive predictive value (PPV) of 83.4%(CI:79.7%, 87.1%) and a negative predictive value (NPV) of 65.8%(CI:61%, 70.5%). The overall accuracy of BAL was 70.5% and the exact concordance was 39%. Our findings suggest that BAL cytology is not sensitive but is a specific test for diagnosis of lung carcinoma. If transbronchial lung biopsy is combined with bronchoalveolar lavage, the positive diagnostic rate will be further elevated.

Lack of response to EGFR tyrosine kinase inhibitors in an amylase-producing lung cancer with a preexisting MET amplification

A 76-year-old man was diagnosed as having lung adenocarcinoma harboring an epidermal growth factor receptor (EGFR)-activating mutation based on a transbronchial biopsy specimen. Although laboratory data showed a marked elevation of saliva-type amylase activity in both the serum and urine, the salivary glands and pancreas were not clinically involved in hyperamylasemia. The patient was treated with EGFR tyrosine kinase inhibitors (EGFR-TKIs). However, the EGFR-TKIs were ineffective, and the patient’s amylase levels increased in parallel with disease progression. He eventually died of respiratory failure. On autopsy, the histological findings showed an invasive adenocarcinoma with micropapillary growth and an immunohistochemical study revealed the localization of the amylase in the cytoplasm of tumor cells. Using fluorescence in situ hybridization analyses of both transbronchial lung biopsy specimens obtained prior to treatment and the autopsied lung tumor, we confirmed the amplification of the MET gene prior to drug exposure. The result suggested that the lung cancer might have overcome the inhibition of EGFR-TKIs via MET amplification. This case report also indicated that the amylase levels of amylase-producing lung cancer vary with disease progression, and hyperamylasemia refractory to EGFR-TKIs may be a predictor of drug resistance to EGFR-TKIs. Therefore, if the amylase levels do not decrease sufficiently in response to EGFR-TKI treatment in patients with EGFR-mutated, amylase-producing lung cancer, the possibility that drug resistance to EGFR-TKIs may coexist with the EGFR mutation should be considered.