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Abstract This study aimed to compare computed tomography (CT) findings between basaloid lung squamous cell carcinoma (SCC) and non-basaloid SCC. From July 2003 to April 2021, 39 patients with surgically proven basaloid SCC were identified. For comparison, 161 patients with surgically proven non-basaloid SCC from June 2018 to January 2019 were selected consecutively. Clinical features, demographic characteristics, and CT findings were compared using chi-square test or Fisher’s exact test except for differences in means for which Student’s t-test was used. Additionally, Mantel-Haenszel test was performed to control the confounding of the presence of cavitation between basaloid and non-basaloid SCCs with tumors stratified by clinical T staging. Compared with patients with non-basaloid SCC, patients with basaloid SCC had significantly (p

Summary: Background: Lung cancer diagnostic guidelines advocate for invasive mediastinal nodal staging (IMNS), but the survival benefits of this approach in patients with non-small cell lung cancer (NSCLC) without radiologic evidence of lymph node metastasis (rN0) remain uncertain. We aimed to investigate the impact of IMNS in patients with rN0 NSCLC by comparing the long-term survival between patients who underwent IMNS and those who did not (non-IMNS). Methods: In this retrospective cohort study, we included patients with NSCLC but without radiologic evidence of lymph node metastasis from the Registry for Thoracic Cancer Surgery and the clinical data warehouse at the Samsung Medical Centre, Republic of Korea between January 2, 2008 and December 31, 2016. We compared the 5-year overall survival (OS) rate as the primary outcome after propensity score matching between the IMNS and non-IMNS groups. The age, sex, performance statue, tumor size, centrality, solidity, lung function, FDG uptake in PET-CT, and histological examination of the tumor before surgery were matched. Findings: A total of 4545 patients (887 in the IMNS group and 3658 in the non-IMNS group) who received curative treatment for NSCLC were included in this study. By the mediastinal node dissection, the overall incidence of unforeseen mediastinal node metastasis (N2) was 7.2% (317/4378 patients). Despite the IMNS, 67% of pathological N2 was missed (61/91 patients with unforeseen N2). Based on propensity score matching, 866 patients each for the IMNS and non-IMNS groups were assigned. There was no significant difference in 5-year OS and recurrence-free survival (RFS) between two groups: 5-year OS was 73.9% (95% confidence interval, CI: 71%–77%) for IMNS and 71.7% (95% CI: 68.6%–74.9%; p = 0.23), for non-IMNS (hazard ratio, HR 0.90, 95% CI: 0.77–1.07), while 5-year RFS was 64.7% (95% CI: 61.5%–68.2%) and 67.5% (95% CI: 64.3%–70.9%; p = 0.35 (HR 1.08, 95% CI: 0.92–1.27), respectively. Moreover, the timing and locations of recurrence were similar in both groups. Interpretation: IMNS might not be required before surgery for patients with NSCLC without LN suspicious of metastasis. Further randomised trials are required to validate the findings of the present study. Funding: None.

Background: Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) that results from an immune-mediated reaction involving various antigens in susceptible individuals. However, the clinical characteristics and outcomes of HP in South Korea are not well understood. Objectives: This study was conducted to identify the clinical characteristics and outcomes of HP in South Korea. Design: This is a retrospective observational study investigating patients with pathologically confirmed HP at our center, along with a comprehensive review of published HP cases in the Republic of Korea. Methods: This retrospective study analyzed 43 patients with pathologically proven HP at a single tertiary hospital in Korea between 1996 and 2020. In addition, case reports of HP published in Korea were collected. The clinical characteristics, etiologies, treatment, and outcomes of patients from our center, as well as case reports, were reviewed. Patients from our hospital were divided into fibrotic and nonfibrotic subtypes according to the ATS/JRS/ALAT guidelines. Results: Among 43 patients with biopsy-proven HP, 12 (27.9%) and 31 (72.1%) patients were classified into the fibrotic and nonfibrotic subtypes, respectively. The fibrotic HP group was older (64.6 ± 8.5 versus 55.2 ± 8.3, p = 0.002) with less frequent complaints of fever (0% versus 45.2%, p = 0.013) compared to the nonfibrotic HP group. The most common inciting antigen was household mold (21, 48.8%), followed by inorganic substances (6, 14.0%). Inciting antigens were not identified in eight (18.6%) patients. Treatment of corticosteroids was initiated in 34 (79.1%) patients. An analysis of 46 patients from Korea by literature review demonstrated that reported cases were relatively younger and drugs were the most common etiology compared to our cohort. Conclusion: The analysis of reported cases, as well as our cohort, showed that exposure history and clinical manifestations are heterogeneous for patients with HP in South Korea.

Abstract Background To understand the molecular mechanisms involved in regulation of DNA methyltransferases (DNMTs) by metformin in non-small cell lung cancer (NSCLC) cells. Methods Expression levels of DNMTs in response to metformin were analyzed in NSCLC cells. MicroRNAs regulating expression of DNMTs at the post-transcriptional level were searched using miRNA-target databases (miRDB and miRTarBase), TCGA RNASeqV2 lung cancer data, and miRNA-seq. Results Metformin dose-dependently downregulated expression of DNMT1 and DNMT3a at the post-transcriptional level and expression of DNMT3b at the transcriptional level in A549 lung cancer cells. Activity of DNMTs was reduced by about 2.6-fold in A549 cells treated with 10 mM metformin for 72 h. miR-148/-152 family members (miR-148a, miR-148b, and miR-152) targeting the 3′UTR of DNMTs were associated with post-transcriptional regulation of DNMTs by metformin. Metformin upregulated expression of miR-148a, miR-148b, and miR-152 in A549 and H1650 cells. Transfection with an miR-148b plasmid or a mimic suppressed expression of DNMT1 and DNMT3b in A549 cells. Transfection with the miR-148a mimic in A549 and H1650 cells decreased the luciferase activity of DNMT1 3′UTR. A combination of metformin and cisplatin synergistically increased expression levels of miR-148/-152 family members but decreased expression of DNMTs in A549 cells. Low expression of miR-148b was associated with poor overall survival (HR = 2.56, 95% CI 1.09—6.47; P = 0.04) but not with recurrence-free survival. Conclusions The present study suggests that metformin inhibits expression of DNMTs by upregulating miR-148/-152 family members in NSCLC cells.

Abstract Pulmonary lymphangitic carcinomatosis (PLC) is associated with a poor prognosis in patients with non-small cell lung cancer (NSCLC). We sought to determine prognostic value of pretherapeutic fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in NSCLC with radiologically diagnosed PLC. We retrospectively reviewed 50 NSCLC patients with radiologically diagnosed PLC. Among eight clinical variables and five imaging parameters, metabolic PLC burden, which represents the overall tumor burden of PLC, and cPLC, which represents the location and extent of PLC in a three-grade system, were used. In multivariate analyses for progression-free survival, metabolic PLC burden (P = 0.0181), cPLC (P = 0.0401), and clinical stage (P = 0.0284) were identified as independent prognostic factors. High metabolic PLC burden had a worse prognosis, and the prognosis of cPLC3 was significantly worse than that of cPLC1 or cPLC2. In univariate analyses for overall survival, only age (P = 0.0073) was identified a prognostic factor. In conclusion, FDG PET/CT parameters were identified as independent prognostic factors in NSCLC with radiologically diagnosed PLC. Furthermore, a combination of anatomical and metabolic information about PLC obtained using FDG PET/CT provides insight into the overall tumor burden of PLC and is useful in predicting prognosis.

Metastasis is a major cause of death in lung cancer patients. Therefore, a deeper understanding of the metastatic mechanisms is important for developing better management strategies for lung cancer patients. This study evaluated the patterns of extrathoracic metastases in lung cancer. We retrieved data for 25,103 lung cancer patients from an institutional database and then evaluated the impacts of clinicopathologic factors on metastasis patterns. We found that 36.5% of patients had extrathoracic metastasis. Younger patients had a significantly higher extrathoracic metastasis rate in most histologic subtypes. Metastases to the bone (58.3%), central nervous system (CNS) (44.3%), liver (26.6%) and adrenal gland (18.3%) accounted for 85.5% of all extrathoracic metastases. Patients with nonmucinous adenocarcinoma had significantly higher bone metastasis rate. Patients with small cell carcinoma and large cell neuroendocrine carcinoma (LCNEC) had significantly higher liver metastasis rates. Further, patients with LCNEC also had a significantly lower bone metastasis rate, and patients with squamous cell carcinoma had a significantly lower CNS metastasis rate. Patients with multiple cancers had similar patterns of metastasis compared to patients with only lung cancer. In conclusion, different histologic subtypes of lung cancer have different metastatic patterns. Our study might help clinicians decide on follow-up strategies.

Abstract Background Endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) is used to evaluate hilar/interlobar/lobar lymph nodes. This study aimed to assess the clinical utility of EBUS‐TBNA for station 10/11/12 lymph nodes (LNs) in patients with primary lung cancer. Methods This was a retrospective analysis of a prospectively collected database of patients with primary lung cancer who underwent EBUS‐TBNA for station 10/11/12 LNs from January 2015 to December 2019. Patients with benign results from EBUS‐TBNA who did not undergo surgical sampling/clinical follow‐up or who received radiotherapy/chemotherapy were excluded. Results The analyses were conducted on 889 LNs from 797 patients. The overall diagnostic sensitivity, specificity, accuracy, negative predictive value (NPV), and positive predictive value of EBUS‐TBNA were 95.7, 100, 97.3, 93.2, and 100%, respectively. Diagnostic sensitivity was significantly lower for LNs

Although the typical CT findings of Pneumocystis jiroveci pneumonia (PJP) include diffuse or multifocal areas of ground-glass opacities in both lungs, it can also rarely manifest as multiple pulmonary nodules. We report a rare case of atypical PJP in an immunocompromised patient with multiple myeloma, presenting as widespread ground-glass opacities and multiple necrotic subpleural nodules in both lungs on CT, which proved to be granulomatous PJP on percutaneous transthoracic needle biopsy.

Vasculitis is a systemic disease, characterized by inflammation of the vascular wall. Although rare, it is sometimes life-threatening due to diffuse pulmonary hemorrhage or acute glomerulonephritis. Besides primary vasculitis, whose cause is unknown, numerous conditions such as autoimmune diseases, drugs, infections, and tumors can cause secondary vasculitis. Vasculitis displays various non-specific symptoms, signs, and laboratory findings; hence, diagnosis of the disease requires integration of various results including clinical features, imaging findings, autoantibody tests, and pathological findings. In this review, we have discussed the clinical, radiologic, and pathological features of vasculitis. Further, we elaborated the imaging findings and differential diagnosis of typical vasculitis that frequently involves the lung and introduced a new international classification of vasculitis, the Diagnostic and Classification Criteria in Vasculitis.

Abstract. Basaloid squamous cell carcinoma (SCC) is very rare subtype of SCC of the lung and it is important to distinguish basaloid to other subtypes of SCCs, since the prognosis of basaloid subtype is considered poorer than that of other non-basaloid subtypes of SCCs. Aim of this study was to assess computed tomography (CT) findings of basaloid SCC of the lung in 12 patients. From January 2016 to April 2021, 12 patients with surgically proven basaloid SCC of the lung were identified. CT findings were analyzed, and the imaging features were compared with histopathologic reports. Clinical and demographic features were also analyzed. Axial location of the tumor was central in 5 patients, while 7 was in peripheral. Of the 7 patients whose tumors were located in the peripheral, margin of the tumor were smooth (n = 2), lobulated (n = 2), or spiculated (n = 3). After contrast injection, net enhancement value ranged from 15.8 to 71.8 HU (median, 36.4 HU). Endobronchial growth were seen in 5 patients and these patients accompanied obstructive pneumonia or atelectasis. Internal profuse necrosis, cavitation, or calcifications were not seen. On CT, basaloid squamous cell presents as solitary nodule or mass with moderate enhancement. Tumor was located either peripheral or central compartment of the lung and cavitation was absent.

Abstract Background Nuclear protein in testis (NUT) carcinoma is a rare tumor associated with NUT rearrangement that can present as poorly differentiated to undifferentiated carcinoma, with or without abrupt squamous differentiation. It is often misdiagnosed as poorly differentiated carcinoma or undifferentiated carcinoma if NUT is not suspected. In this study, we retrospectively analyzed pulmonary NUT carcinoma cases diagnosed with NUT immunohistochemical staining and discuss the differential diagnosis to provide information for this rare and aggressive entity. Methods Cases, diagnosed as “NUT carcinoma” in lung pleura and “metastatic NUT carcinoma from the lung” in lymph nodes were diagnosed between 2017 and 2019 at the Samsung Medical Center (SMC). Clinical features such as age, sex, treatment and follow‐up period, and pathological reports were obtained by reviewing patients’ electronic medical records. Results A total of 10 NUT carcinoma cases were found in the SMC pathology database. Seven patients were men and six were non‐smokers. Tumor cells showed various cellular features such as round, squamoid, and spindle. Some cases had initially been misdiagnosed as spindle cell neoplasm, round cell sarcoma, squamous cell carcinoma and small cell carcinoma. All cases showed diffuse strong nuclear expression of NUT immunohistochemical staining, and some were positive for p63 staining and negative for CD56 staining. Conclusions NUT carcinoma is often misdiagnosed because of its various morphologies. It is important to consider NUT as one of the differential diagnoses when encountering lung biopsy with undifferentiated morphology. Key points Due to various morphological features, NUT carcinoma can be misdiagnosed It is important to consider NUT carcinoma when diagnosing a poorly differentiated or undifferentiated tumor

Aim: Several studies have reported favorable outcomes of nonspecific interstitial pneumonia (NSIP); however, its prognosis and prognostic factors remain unclear. This study aimed to determine the outcomes of fibrotic NSIP and the prognostic factors for progression, relapse, and survival. Methods: In this retrospective study, we reviewed the clinical data of 204 patients diagnosed with fibrotic NSIP by surgical lung biopsy at Samsung Medical Center. The factors associated with survival and disease progression or relapse were determined using Cox proportional hazard analysis. Results: The median age of patients was 54 years and 67 (33%) patients were male. Also, 47 patients (23%) were current or ex-smokers. In all, 141 (69%) patients were diagnosed with idiopathic NSIP, while 63 (31%) patients were associated with connective tissue diseases. Progression or relapse was observed in 100 (49%) patients. The 5-year and 10-year survival rates were 94.6% and 90.4%, respectively. The factors associated with disease progression and relapse were diffusing capacity for carbon monoxide (DLco) 15% (adjusted HR, 0.592; 95% CI, 0.352–0.994; p = 0.047), and treatment with corticosteroid and azathioprine (adjusted HR, 0.556; 95% CI, 0.311–0.955; p = 0.048). Disease progression or relapse was associated with mortality (adjusted HR, 7.135; 95% CI, 1.499–33.971; p = 0.014). Conclusion: Preserved lung function, BAL lymphocytosis, and treatment with corticosteroids and azathioprine were associated with lower risks of disease progression and relapse, which were risk factors for mortality.

Connective tissue diseases (CTDs) demonstrating features of interstitial lung disease (ILD) include systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), dermatomyositis (DM) and polymyositis (PM), ankylosing spondylitis (AS), Sjogren syndrome (SS), and mixed connective tissue disease (MCTD). On histopathology of lung biopsy in CTD-related ILDs (CTD-ILDs), multi-compartment involvement is an important clue, and when present, should bring CTD to the top of the list of etiologic differential diagnoses. Diverse histologic patterns including nonspecific interstitial pneumonia (NSIP), usual interstitial pneumonia (UIP), organizing pneumonia, apical fibrosis, diffuse alveolar damage, and lymphoid interstitial pneumonia can be seen on histology in patients with CTD-ILDs. Although proportions of ILDs vary, the NSIP pattern accounts for a large proportion, especially in SSc, DM and/or PM and MCTD, followed by the UIP pattern. In RA patients, interstitial lung abnormality (ILA) is reported to occur in approximately 20–60% of individuals of which 35–45% will have progression of the CT abnormality. Subpleural distribution and greater baseline ILA involvement are risk factors associated with disease progression. Asymptomatic CTD-ILDs or ILA patients with normal lung function and without evidence of disease progression can be followed without treatment. Immunosuppressive or antifibrotic agents for symptomatic and/or fibrosing CTD-ILDs can be used in patients who require treatment.

IgG4-related disease is a systemic inflammatory disease and is known as IgG4-related lung disease (IgG4-RLD) when it involves the respiratory system. Primary lung cancer arising from a background of IgG4-RLD is very rare. Herein, we report a case of adenosquamous carcinoma arising from the background of IgG4-RLD and presenting as an interstitial lung disease pattern. A 66-year-old man underwent lobectomy under the impression of primary lung cancer. Grossly, the mass was ill-defined and gray-tan colored, and the background lung was fibrotic. Microscopically, tumor cells showed both squamous and glandular differentiation. Dense lymphoplasmacytic infiltration with fibrosis and obliterative phlebitis were seen in the background lung. IgG4 immunohistochemical stain showed diffuse positivity in infiltrating plasma cells. Primary lung adenosquamous carcinoma has not been reported in a background of IgG4-RLD. Due to the rarity of IgG4-RLD, physicians must follow patients with IgG4-RLD over long periods of time to accurately predict the risk of lung cancer.

The aim of this study was to evaluate the CT and PET-CT features of solitary pulmonary capillary hemangioma (SPCH) with clinicopathologic correlations. This retrospective study included 17 patients with histologically proven SPCH from four tertiary institutions. The clinical, pathological and imaging findings of SPCH were reviewed. The CT features assessed included lesion location, size, density, contour, margin, enhancement, presence of air bronchogram, perivascular lucency and pleural retraction, and 18F-fluorodeoxyglucose uptake on PET-CT. Changes in the size during the follow-up period were also evaluated. Imaging features were correlated with the clinicopathologic findings. The mean age of the patients was 47 years (range 30–60 years). All SPCHs were incidentally detected during screening CT examinations (n = 13, 76%) or during cancer work-up (n = 4, 24%). Most SPCHs appeared as part-solid nodules (n = 15, 88%), the remaining appeared as a pure ground-glass nodule or a pure solid nodule, respectively. Most had smooth contours (n = 16, 94%), while one had a lobulated contour. Nine SPCHs (53%) showed ill-defined margins. Air bronchogram was present in ten (59%) SPCHs, and perivascular lucency in two (12%). All SPCHs exhibited hypoattenuation on contrast-enhanced CT and hypometabolism on PET-CT. During the follow-up period (mean 14.8 ± 17.7 months), the lesions showed no change in size or density in ten SPCHs (59%), decreased or fluctuation in size and density in three (18%). SPCH is often incidentally detected in young and middle-aged adults, commonly as an ill-defined part-solid nodule that may accompany air bronchogram, perivascular lucency, and fluctuation in size or density on CT and hypometabolism on PET-CT.

This review article aims to address mysteries existing between Interstitial Lung Abnormality (ILA) and Nonspecific Interstitial Pneumonia (NSIP). The concept and definition of ILA are based upon CT scans from multiple large-scale cohort studies, whereas the concept and definition of NSIP originally derived from pathology with evolution to multi-disciplinary diagnosis. NSIP is the diagnosis as Interstitial Lung Disease (ILD) with clinical significance, whereas only a part of subjects with ILA have clinically significant ILD. Eventually, both ILA and NSIP must be understood in the context of chronic fibrosing ILD and progressive ILD, which remains to be further investigated.

The connective tissue diseases (CTDs) demonstrating features of interstitial lung disease (ILD) include systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), progressive systemic sclerosis (PSS), dermatomyositis (DM) and polymyositis (PM), ankylosing spondylitis (AS), Sjogren’s syndrome (SS), and mixed connective tissue disease (MCTD). In RA patients in particular, interstitial lung abnormality (ILA) (of varying degrees; severe vs. mild) is reported to occur in approximately 20–60 % of individuals and CT disease progression occurs in approximately 35–45 % of them. The ILAs have been associated with a spectrum of functional and physiologic decrement. The identification of progressive ILA may enable appropriate surveillance and the commencement of treatment with the goal of improving morbidity and mortality rates of established RA-ILD. Subpleural distribution and higher baseline ILA/ILD extent were risk factors associated with disease progression. At histopathologic analysis, connective tissue disease-related interstitial lung diseases (CTD-ILDs) are diverse and include nonspecific interstitial pneumonia (NSIP), usual interstitial pneumonia (UIP), organizing pneumonia (OP), apical fibrosis, diffuse alveolar damage (DAD), and lymphoid interstitial pneumonia (LIP). Even though proportions of ILDs vary, NSIP pattern accounts for a large proportion, especially in PSS, DM/PM and MCTD, followed by UIP pattern. Evidence has been published that treatment of subclinical CT lung abnormalities showing a tendency to progress to ILD may stabilize the CT alterations. The identification of subclinical lung abnormalities can be appropriate in the management of the disease and CT appears to be the gold standard for the evaluation of lung parenchyma.

Introduction: To demonstrate semantic, radiomics, and the combined risk models related to the prognoses of pulmonary pleomorphic carcinomas (PCs). Methods: We included 85 patients (M:F = 71:14; age, 35–88 [mean, 63 years]) whose imaging features were divided into training (n = 60) and test (n = 25) sets. Nineteen semantic and 142 radiomics features related to tumors were computed. Semantic risk score (SRS) model was built using the Cox-least absolute shrinkage and selection operator (LASSO) approach. Radiomics risk score (RRS) from CT and PET features and combined risk score (CRS) adopting both semantic and radiomics features were also constructed. Risk groups were stratified by the median of the risk scores of the training set. Survival analysis was conducted with the Kaplan-Meier plots. Results: Of 85 PCs, adenocarcinoma was the most common epithelial component found in 63 (73 %) tumors. In SRS model, four features were stratified into high- and low-risk groups (HR, 4.119; concordance index ([C-index], 0.664) in the test set. In RRS model, five features helped improve the stratification (HR, 3.716; C-index, 0.591) and in CRS model, three features helped perform the best stratification (HR, 4.795; C-index, 0.617). The two significant features of CRS models were the SUVmax and the histogram feature of energy ([CT Firstorder Energy]). Conclusion: In PCs of the lungs, the combined model leveraging semantic and radiomics features provides a better prognosis compared to using semantic and radiomics features separately. The high SUVmax of solid portion (CT Firstorder Energy) of tumors is associated with poor prognosis in lung PCs.

Cytologic diagnosis of nuclear protein in testis (NUT) midline carcinoma (NMC) is important due to its aggressive behavior and miserable prognosis. Early diagnosis of NMC can facilitate proper management, and here we report two rare cases of thoracic NMC with cytohistologic correlation. In aspiration cytology, the tumor presented with mixed cohesive clusters and dispersed single cells, diffuse background necrosis and many neutrophils. Most of the tumor cells had scanty cytoplasm and medium-sized irregular nuclei, which had fine to granular nuclear chromatin. Interestingly, a few dyskeratotic cells or squamoid cell clusters were present in each case. Biopsy specimen histology revealed more frequent squamous differentiation, and additional immunohistochemistry tests showed nuclear expression of NUT. Because this tumor has a notorious progression and has been previously underestimated in terms of its prevalence, awareness of characteristic findings and proper ancillary tests should be considered in all suspicious cases.

Pulmonary infection is a major cause of mortality in immunocompromised patients. Immunosuppression can be divided into neutropenia, humoral immunodeficiency, and cellular immunodeficiency. Pulmonary infection in these patients typically depends on the type, duration, and degree of immunodeficiency. Pulmonary infection in immunocompromised patients is often nonspecific, both clinically and radiologically, but a certain type of pulmonary infection may provide typical radiological features helpful for definitive diagnosis. Therefore, it is essential to incorporate clinical information into radiological features to narrow down the differential diagnosis and to potentially reduce the morbidity and mortality associated with pulmonary infections in immunocompromised patients.

Morphologically pneumonia is usually classified into lobar pneumonia, bronchopneumonia, and interstitial pneumonia. Chronic pneumonia is also a kind of pneumonia in immunocompetent and mildly immunocompromised patients. Specific organisms may be involved in community-acquired pneumonia (CAP) according to patients’ age or underlying conditions. The organisms involved in CAP are different from those in hospital-acquired pneumonia. Mixed pneumonia includes septic pneumonia, lung abscess, and focal organizing pneumonia. The role of imaging in pneumonia includes the detection or exclusion of the presence of pneumonia, narrowing down of differential diagnosis of the pneumonia from other lung conditions, planning of further diagnostic procedure, and the assessment of treatment response with follow-up studies. New drugs for pneumonia are expected to open a door widely for antibiotic treatment for various pneumonias.

Background Pulmonary nodular lymphoid hyperplasia (PNLH) is a non-neoplastic pulmonary lymphoid disorder that can be mistaken for malignancy on radiography. Herein, we present nine cases of PNLH, emphasizing clinicoradiological findings and histological features. Methods We analyzed radiological and clinicopathological features from the electronic medical records of nine patients (eight females and one male) diagnosed with PNLH. IgG and IgG4 immunohistochemical staining was performed in three patients. Results Two of the nine patients had experienced tuberculosis 40 and 30 years prior, respectively. Interestingly, none were current smokers, although two were ex-smokers. Three patients complaining of persistent cough underwent computed tomography of the chest. PNLH was incidentally discovered in five patients during examination for other reasons. The remaining patient was diagnosed with the disease following treatment for pneumonia. Imaging studies revealed consolidation or a mass-like lesion in eight patients. First impressions included invasive adenocarcinoma and mucosal-associated lymphoid tissue‒type lymphoma. Aspergillosis was suspected in the remaining patient based on radiological images. Resection was performed in all patients. Microscopically, the lesions consisted of nodular proliferation of reactive germinal centers accompanied by infiltration of neutrophils and macrophages in various degrees and surrounding fibrosis. Ultimately, all nine patients were diagnosed with PNLH and showed no evidence of recurrence on follow-up. Conclusions PNLH is an uncommon but distinct entity with a benign nature, and understanding the radiological and clinicopathological characteristics of PNLH is important.

Abstract Background The objective of this study was to discover DNA methylation biomarkers for detecting non-small lung cancer (NSCLC) in bronchial washings and understanding the association between DNA methylation and smoking cessation. Methods DNA methylation was analyzed in bronchial washing samples from 70 NSCLCs and 53 hospital-based controls using Illumina HumanMethylation450K BeadChip. Methylation levels in these bronchial washings were compared to those in 897 primary lung tissues of The Cancer Genome Atlas (TCGA) data. Results Twenty-four CpGs (p

Molecular evaluation of EGFR mutation is indispensable in treating non-small cell lung cancer (NSCLC). We compared the results of EGFR analysis using tissue DNA (tDNA) and circulating tumor (ctDNA) to evaluate the feasibility of plasma as an effective material for detecting EGFR mutation and the reliability of ctDNA analysis in real-world practice settings. We enrolled 554 NSCLC cases who had undergone ctDNA EGFR analysis between January 2019 and March 2020. EGFR mutations were detected in 240 (57.3%) of the 421 cases with EGFR mutations confirmed by tDNA analysis. In multivariate analysis, the size of the largest tumor deposits, disease progression, M stage, the detectable amount of tumor tissue with EGFR mutation in distant metastasis, liver metastasis, pleural seeding, and bone metastasis (p < 0.05) were identified as independent factors affecting the detection rate of EGFR mutations in ctDNA. Survival analysis revealed ctDNA status and M stage (p < 0.001) to be independent predictors of overall survival in the multivariate analysis. Our study demonstrates that EGFR analysis using ctDNA is a useful clinical tool and can aid in therapeutic decisions in real-world practical settings. However, clinicians should be aware of the possibility of false negatives and confirm EGFR analysis using tDNA in certain situations.

Abstract Background This study was aimed at understanding whether bronchial biopsy specimen can be used as a surrogate for DNA methylation analysis in surgically resected lung cancer. Methods A genome-wide methylation was analyzed in 42 surgically resected tumor tissues, 136 bronchial washing, 12 sputum, and 8 bronchial biopsy specimens using the Infinium HumanMethylation450 BeadChip, and models for prediction of lung cancer were evaluated using TCGA lung cancer data. Results Four thousand seven hundred and twenty-six CpGs (P 0.05, Wilcoxon rank-sum test). However, their methylation levels were significantly different between paired bronchial biopsy and washing (P

Thymic adenocarcinoma is extremely rare. Although its histologic features have been occasionally reported, a lack of description of the cytologic features has hampered the prompt and accurate diagnosis of this condition. Herein, we describe the cytologic findings and histology of four aspiration cytology specimens of thymic adenocarcinoma. The specimens were obtained from primary tumors, metastatic lymph nodes, and pericardial effusions. All four specimens showed three-dimensional glandular clusters with a loss of polarity and nuclear overlapping. One specimen had extensive extracellular mucinous material. Three specimens contained tumor cells with intracytoplasmic vacuoles. While the specimen with extracellular mucin showed relatively mild cytologic atypia, other specimens exhibited more atypical cytologic changes: irregular nuclear membranes, a coarse chromatin pattern, and prominent nucleoli. The cytologic features were correlated with the histologic features in each case of enteric type thymic adenocarcinoma. The differential diagnosis included other thymic carcinomas, yolk sac tumors, and metastatic adenocarcinoma from the lung or colorectum.

Pleural involvement of amyloidosis is rare and usually manifested as persistent massive effusion. However, it may present as pleural nodules or plaques without massive effusion. A 55-year-old man was referred for abnormalities of chest radiography and the computed tomography (CT) exam revealed multiple pleural nodules without effusion in the left hemithorax. The radiologic impression was pleural malignancy, and whole body 18F-fluorodeoxyglucose positron emission tomography-CT exam was performed. Not only corresponding pleural nodules but also other areas along the left pleura were hypermetabolic, whereas no hypermetabolic lesions were noted outside of the thorax. Preoperative diagnosis was made as malignant mesothelioma. During left pleuropneumonectomy, multiple hard whitish nodules or plaques were found along the pleura, and which were proven to amyloidosis on frozen section. The patient underwent not left pleuropneumonectomy but folup. Because of difficulty of accurate diagnosis, we report the localized pleural amyloidosis for awareness of the disease.

IntroductionThe maximum standardized uptake value (SUVmax) in 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) may be of prognostic significance for patients with malignant pleural mesothelioma (MPM). This retrospective study aimed to investigate the prognostic value of the SUVmax in patients with MPM.Materials and methodsMedical records were retrospectively reviewed for the patients who were diagnosed with histopathologically proven MPM between 2009 and 2018 at Samsung Medical Center. For each patient, SUVmax was calculated for the primary lesion on PET/CT. To determine optimal cutoff values for predicting mortality, receiver operating characteristic curves were used.ResultsAmong the 54 study patients, 34 (63.0%) had epithelioid subtype, 13 (24.1%) had sarcomatoid or biphasic subtype, and 7 (13.0%) had mesothelioma, not otherwise specified (NOS). The median overall survival (OS) was 8.7 months, and the median SUVmax was 9.9. The median values of SUVmax were 5.5 in patients with epithelioid subtype, 11.7 in those with sarcomatoid/biphasic subtype, and 13.3 in those with NOS subtype (P = 0.003). The optimal cutoff values of SUVmax to predict mortality were 10.1 in all patients, and 8.5 in patients with epithelioid subtype. In multivariate analysis, SUVmax was significantly associated with overall survival in all patients (P = 0.003) and in patients with epithelioid subtype (P = 0.012), but not in those with non-epithelioid subtype.ConclusionsSUVmax in PET/CT is an independent prognostic factor in patients with MPM, especially those with epithelioid subtype. The histologic subtype of MPM should be considered when evaluating the prognostic significance of SUVmax.

Malignant pulmonary granular cell tumor (GCT) is extremely rare and difficult to distinguish from benign GCT. Most GCTs are neural-type and express S-100. However, a small subset of tumors sub-classified as the non-neural type do not express S-100. We report a case of malignant non-neural-type GCT in the lungs.A 77-year-old woman felt chest discomfort and dyspnea in July 2019. She had never smoked and had no medical history other than hypertension and diabetes mellitus.She was initially evaluated at a local hospital. Flexible bronchoscopy showed total occlusion of the right main bronchus by a mass-like lesion. Biopsy of the mass lesion revealed chronic inflammation. The patient visited for re-evaluation in September 2019. Rigid bronchoscopy showed worsening of the total obstruction of the right main bronchus by a tumor mass, such that the carina was not visible. Additionally, endobronchial nodules were observed on the medial side of left main bronchus. The tumor masses of both main bronchi were removed by bronchoscopic intervention, but the right main bronchus was not opened. Biopsy revealed malignant GCT, favoring the non-neuronal type (S-100-negative).We report an extremely rare case of malignant pulmonary GCT negative for S-100 in immunohistochemistry. In this case, surgical resection was not possible because the tumor was diagnosed at a fairly advanced stage and had spread to involve the contralateral main bronchus. The patient chose to be treated at another hospital and was thereafter lost to follow-up. Keywords: Malignant pulmonary granular cell tumor, S-100-Negative, Non-neural type

Pulmonary sclerosing pneumocytoma is a rare, benign lung tumor commonly seen in women in the fifth decade of life. It usually manifests as a solitary, well-circumscribed juxtapleural nodule or mass with intense, homogeneous enhancement on computed tomography scans. Herein, we report a case of sclerosing pneumocytoma presenting as main nodule with satellite nodules, mimicking tuberculosis.

Background We reviewed a series of 188 resected pulmonary mucinous adenocarcinomas (MAs) to clarify the prognostic significance of lepidic and non-lepidic patterns. Methods Non-lepidic patterns were divided into bland, non-distorted acini with uncertain invasiveness (pattern 1), unequivocal invasion into stroma (pattern 2), or invasion into alveolar spaces (pattern 3). Results The mean proportion of invasive patterns (patterns 2 and 3) was lowest in small (≤ 3 cm) tumors, and gradually increased in intermediate (> 3 cm and ≤ 7 cm) and large (> 7 cm) tumors (8.4%, 34.3%, and 50.1%, respectively). Adjusted T (aT) stage, as determined by the size of invasive patterns, was positively correlated with adverse histologic and clinical features including older age, male sex, and ever smokers. aTis tumors, which were exclusively composed of lepidic pattern (n = 9), or a mixture of lepidic and pattern 1 (n = 40) without any invasive patterns, showed 100% disease- free survival (DFS). The aT1mi tumors, with minimal (≤ 5 mm) invasive patterns (n = 63), showed a 95.2% 5-year DFS, with recurrences (n = 2) limited to tumors greater than 3 cm in total size (n = 23). Both T and aT stage were significantly associated with DFS; however, survival within the separate T-stage subgroups was stratified according to the aT stage, most notably in the intermediatestage subgroups. In multivariate analysis, the size of invasive patterns (p = .020), pleural invasion (p < .001), and vascular invasion (p = .048) were independent predictors of recurrence, whereas total size failed to achieve statistical significance (p = .121). Conclusions This study provides a rationale for histologic risk stratification in pulmonary MA based on the extent of invasive growth patterns with refined criteria for invasion.

Pulmonary arteriovenous fistula (PAVF) is abnormally dilated vessels that provide a right-to-left shunt between pulmonary artery and pulmonary vein and is clinically divided into simple and complex type. Here, we report four cases of surgically resected sporadic PAVFs presenting various clinical and histologic spectrums. Cases 1 (a 57-old-female) and 2 (a 54-old-female) presented as incidentally identified single aneurysmal fistulas and the lesions were surgically removed without complication. On the other hand, case 3 (an 11-old-male) showed diffuse dilated vascular sacs involving both lungs and caused severe hemodynamic and pulmonary dysfunction. Embolization and surgical resection of the main lesion failed to relieve the symptoms. Case 4 (a 36-old-male) had a localized multiloculated cyst clinically mimicking congenital cystic adenomatoid malformation. Microscopically, the lesion consisted of dilated thick vessels, consistent with the diagnosis of fistulous arteriovenous malformation/hemangioma.

Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are considered the first line treatment for a subset of EGFR-mutated non-small cell lung cancer (NSCLC) patients. Although transformation to small cell lung cancer (SCLC) is one of the known mechanisms of resistance to EGFR TKIs, it is not certain whether transformation to SCLC is exclusively found as a mechanism of TKI resistance in EGFR-mutant tumors. Methods: We identified six patients with primary lung adenocarcinoma that showed transformation to SCLC on second biopsy (n = 401) during a 6-year period. Clinicopathologic information was analyzed and EGFR mutation results were compared between initial and second biopsy samples. Results: Six patients showed transformation from adenocarcinoma to SCLC, of which four were pure SCLCs and two were combined adenocarcinoma and SCLCs. Clinically, four cases were EGFR-mutant tumors from non-smoking females who underwent TKI treatment, and the EGFR mutation was retained in the transformed SCLC tumors. The remaining two adenocarcinomas were EGFR wild-type, and one of these patients received EGFR TKI treatment. Conclusions: NSCLC can acquire a neuroendocrine phenotype with or without EGFR TKI treatment.

Background: Although epidermal growth factor receptor (EGFR), v-Ki-ras2 Kirsten rat sarcoma viral oncogene (KRAS), and anaplastic lymphoma kinase (ALK) mutations in non-small cell lung cancer (NSCLC) were thought to be mutually exclusive, some tumors harbor concomitant mutations. Discovering a driver mutation on the basis of morphologic features and therapeutic responses with mutation analysis can be used to understand pathogenesis and predict resistance in targeted therapy. Methods: In 6,637 patients with NSCLC, 12 patients who had concomitant mutations were selected and clinicopathologic features were reviewed. Clinical characteristics included sex, age, smoking history, previous treatment, and targeted therapy with response and disease-free survival. Histologic features included dominant patterns, nuclear and cytoplasmic features. Results: All patients were diagnosed with adenocarcinoma and had an EGFR mutation. Six patients had concomitant KRAS mutations and the other six had KRAS mutations. Five of six EGFR-KRAS mutation patients showed papillary and acinar histologic patterns with hobnail cells. Three of six received EGFR tyrosine kinase inhibitor (TKI) and showed partial response for 7–29 months. All six EGFR-ALK mutation patients showed solid or cribriform patterns and three had signet ring cells. Five of six EGFR-ALK mutation patients received EGFR TKI and/or ALK inhibitor and four showed partial response or stable disease, except for one patient who had acquired an EGFR mutation. Conclusions: EGFR and ALK mutations play an important role as driver mutations in double mutated NSCLC, and morphologic analysis can be used to predict treatment response.

Thoracolithiasis is a rare benign condition with mobile free bodies in the pleural cavity. It is asymptomatic and mostly found incidentally. Up to our knowledge there is no report of symptomatic numerous thoracolithiasis. We report a very rare case of thoracolithiasis in a 36-year-old female with chest discomfort. Images from computed tomography presented a chain of small non-enhancing nodules in the left hemi-diaphragmatic pleura. Exploratory thoracoscopy was performed and twenty-five mobile pearl like thoracolithiasis were discovered. Histopathology showed extensive necrotic fatty tissue at its center surrounded by fibrosis. The patient was symptom-free after the surgical removal of numerous thoracolithiasis, suggesting thoracolithiasis was associated with chest discomfort. Keywords: Thoracolithiasis, Pleural stone, Pleurolith, Intrathoracic calculus, Intrapleural loose body