2021 WHO Classification of Lung Cancer: Molecular Biology Research and Radiologic-Pathologic Correlation.

The 2021 World Health Organization (WHO) classification system for thoracic tumors (including lung cancer) contains several updates to the 2015 edition. Revisions for lung cancer include a new grading system for invasive nonmucinous adenocarcinoma that better reflects prognosis, reorganization of squamous cell carcinomas and neuroendocrine neoplasms, and description of some new entities. Moreover, remarkable advancements in our knowledge of genetic mutations and targeted therapies have led to a much greater emphasis on genetic testing than that in 2015. In 2015, guidelines recommended evaluation of only two driver mutations, ie, epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) fusions, in patients with nonsquamous non-small cell lung cancer. The 2021 guidelines recommend testing for numerous additional gene mutations for which targeted therapies are now available including ROS1, RET, NTRK1-3, KRAS, BRAF, and MET. The correlation of imaging features and genetic mutations is being studied. Testing for the immune biomarker programmed death ligand 1 is now recommended before starting first-line therapy in patients with metastatic non-small cell lung cancer. Because 70% of lung cancers are unresectable at patient presentation, diagnosis of lung cancer is usually based on small diagnostic samples (ie, biopsy specimens) rather than surgical resection specimens. The 2021 version emphasizes differences in the histopathologic interpretation of small diagnostic samples and resection specimens. Radiologists play a key role not only in evaluation of tumor and metastatic disease but also in identification of optimal biopsy targets. ©RSNA, 2024 Test Your Knowledge questions in the supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article.

Clinical features of CDK4/6 inhibitor-related interstitial lung disease in patients with breast cancer: a case series study.

BACKGROUND: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are the standard treatment for advanced hormone receptor-positive breast cancer. Although interstitial lung disease is a rare (1-3.3%) but serious adverse event associated with CDK4/6 inhibitors, the incidence of interstitial lung disease in Japanese patients in the real world and the risk factors of interstitial lung disease are not clear. METHODS: We retrospectively investigated the incidence of interstitial lung disease in 224 patients with advanced breast cancer who received CDK4/6 inhibitors at our hospital between 31 January 2017 and 31 January 2021. The correlation of age (>50 vs ≤50 years), presence or absence of previous history of interstitial lung disease, lung metastasis, smoking history and chest radiation with the development of interstitial lung disease was evaluated. RESULTS: In total, 177 cases received palbociclib, 39 cases received abemaciclib and 8 cases received both palbociclib and abemaciclib, constituting a palbociclib group (n = 185) and an abemaciclib group (n = 47). At a median observation period of 607 days, 8.0% (18/224) cases (13 definite and 5 probable cases) had interstitial lung disease; 6.5% (12/185) of palbociclib-treated and 13% (6/47) of abemaciclib-treated cases. The median time to interstitial lung disease onset was 178 (range, 14-750) days. There was no significant correlation between the background factors studied and the development of interstitial lung disease. CONCLUSION: The frequency of CDK4/6 inhibitor-induced interstitial lung disease was higher than that reported in clinical trials. We did not identify any risk factors for the development of interstitial lung disease in this study, and thus, larger studies that include patient predisposition are required.

Multiacquisition Variable-Resonance Image Combination Selective Can Improve Image Quality and Reproducibility for Metallic Implants in the Lumbar Spine.

The aim of this study is to evaluate how metallic artifacts in the lumbar spine can affect images obtained from magnetic resonance (MR) sequences. We performed a phantom experiment by scanning an agar containing an orthopedic metallic implant using 64-channel multidetector row computed tomography (CT) and a 3-tesla MR unit. We compared the reproducibility in each measurement, enlargement or reduction ratio of the CT and MR measurements, and signal deviation in each voxel from the control. The reproducibility on CT and multiacquisition variable-resonance image combination selective (MAVRIC SL) was good, but that on the other MR sequences showed either fixed bias or proportional bias. The reduction ratios of the distance between the nails were significantly smaller in MAVRIC SL than in the other MR sequences after CT measurements (p<0.001, respectively). MAVRIC SL was able to reduce the metallic artifact, permitting observation of the tissue surrounding the metal with good reproducibility.

Molecular and cellular studies evaluating a potent 2-cyanoindolizine catechol diether NNRTI targeting wildtype and Y181C mutant HIV-1 reverse transcriptase.

The development of efficacious NNRTIs for HIV/AIDS therapy is commonly met with the emergence of drug resistant strains, including the Y181C variant. Using a computationally-guided approach, we synthesized the catechol diether series of NNRTIs, which display sub-nanomolar potency in cellular assays. Among the most potent were a series of 2-cyanoindolizine substituted catechol diethers, including Compound 1. We present here a thorough evaluation of this compound, including biochemical, cellular, and structural studies. The compound demonstrates low nanomolar potency against both WT and Y181C HIV-1 RT in in vitro and cellular assays. Our crystal structures of both the wildtype and mutant forms of RT in complex with Compound 1 allow the interrogation of this compound's features that allow it to maintain strong efficacy against the drug resistant mutant. Among these are compensatory shifts in the NNRTI binding pocket, persistence of multiple hydrogen bonds, and van der Waals contacts throughout the binding site. Further, the fluorine at the C6 position of the indolizine moiety makes multiple favorable interactions with both RT forms. The present study highlights the indolizine-substituted catechol diether class of NNRTIs as promising therapeutic candidates possessing optimal pharmacological properties and significant potency against multiple RT variants.

DRONE: Direct Tracking of DNA Cytidine Deamination and Other DNA Modifying Activities.

Enzymes that catalyze DNA modifying activities including cytidine deamination and cytosine methylation play important biological roles and have been implicated pathologically in diseases such as cancer. Here, we report Direct Resolution of ONE dalton difference (DRONE), an ultra high performance liquid chromatography (UHPLC)-based analytical method to track a single dalton change in the cytosine-to-uracil conversion catalyzed by the human apolipoprotein B m-RNA editing catalytic polypeptide-like 3 (APOBEC3) cytidine deaminases, implicated in cancer and antiviral defense. Additionally, we demonstrate broad applicability by tracking other important DNA modifications and assessing epigenetic enzyme inhibition. We have extended our methodology to obtain data on two distinct deamination events in the same oligonucleotide substrate designed from a putative APOBEC substrate, diversifying the utility of the described method. DRONE provides an important foundation for in-depth analysis of DNA-modifying enzymes and versatile detection of novel DNA modifications of interest.

Roles of the apparent diffusion coefficient and tumor volume in predicting tumor grade in patients with choroid plexus tumors.

PURPOSE: To explore the utility of the apparent diffusion coefficient (ADC) and tumor volume to predict histological grade and prognosis in patients with choroid plexus tumors. METHODS: ADC and tumor volumes were retrospectively evaluated in 25 patients with choroid plexus papilloma (CPP; WHO grade 1 [n = 13]), atypical CPP (aCPP; grade 2 [n = 8]), or choroid plexus carcinoma (grade 3 [n = 4]) The prognostic roles of ADC and tumor volume were assessed. RESULTS: There were significant differences in mean and minimum ADC values, and tumor volume among the WHO grades (p = 0.033, p = 0.044, and p = 0.014, respectively). Receiver-operating characteristic analysis revealed a mean cutoff ADC value ≤ 1.397 × 10-3 mm2/s for aCPP (sensitivity = 0.667, specificity = 0.923). Multiple linear regression analysis demonstrated that both mean ADC (ß = - 0.455, p = 0.005) and tumor volume (ß = 0.513, p = 0.002) were correlated with WHO grade (adjusted R2 = 0.520, p = 0.005). Kaplan-Meier curve analysis identified poorer survival in patients with WHO grade 2 and 3 tumors than in those with WHO grade 1 disease (p = 0.049 and p = 0.012, respectively). A mean ADC ≤ 1.397 × 10-3 mm2/s (p = 0.001) and tumor volume 21.05 ml (p = 0.031) predicted significantly poorer survival. CONCLUSION: Mean ADC and tumor volume were correlated with WHO grade of choroid plexus tumors. A lower ADC value and a larger tumor volume predicted a poorer prognosis.

Identification of a fungal 1,8-cineole synthase from Hypoxylon sp. with specificity determinants in common with the plant synthases.

Terpenes are an important and diverse class of secondary metabolites widely produced by fungi. Volatile compound screening of a fungal endophyte collection revealed a number of isolates in the family Xylariaceae, producing a series of terpene molecules, including 1,8-cineole. This compound is a commercially important component of eucalyptus oil used in pharmaceutical applications and has been explored as a potential biofuel additive. The genes that produce terpene molecules, such as 1,8-cineole, have been little explored in fungi, providing an opportunity to explore the biosynthetic origin of these compounds. Through genome sequencing of cineole-producing isolate E7406B, we were able to identify 11 new terpene synthase genes. Expressing a subset of these genes in Escherichia coli allowed identification of the hyp3 gene, responsible for 1,8-cineole biosynthesis, the first monoterpene synthase discovered in fungi. In a striking example of convergent evolution, mutational analysis of this terpene synthase revealed an active site asparagine critical for water capture and specificity during cineole synthesis, the same mechanism used in an unrelated plant homologue. These studies have provided insight into the evolutionary relationship of fungal terpene synthases to those in plants and bacteria and further established fungi as a relatively untapped source of this important and diverse class of compounds.

Ratios of peripheral-to-central airway lumen area and percentage wall area as predictors of severity of chronic obstructive pulmonary disease.

OBJECTIVE: The purpose of this study was to assess the ability of the ratios of peripheral-to-central airway lumen area (hereafter referred to as LA) and percentage wall area (hereafter referred to as %WA) to predict the severity of chronic obstructive pulmonary disease (COPD) according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. SUBJECTS AND METHODS: We examined 32 patients (27 men and five women; mean age ± SD, 70.0 ± 6.8 years; seven GOLD stage 0 [at risk for COPD], 19 GOLD stage 1-2 [mild to moderate airflow limitation], and six GOLD stage 3-4 [severe to very severe airflow limitation]) using inspiratory CT. Mean LA and %WA were measured for the first (main bronchi), third, and fifth generations of five bronchi in each lobe and the ratios of peripheral to central airways were calculated (third to first, fifth to first, and fifth to third) and statistically compared. RESULTS: The fifth-generation LA, LA fifth to first, and LA fifth to third significantly decreased and fifth %WA, %WA fifth to first, and %WA fifth to third also increased with progression of GOLD stage (p < 0.05), but central measurements, including first and third generations, did not. There were significant differences between GOLD 0 and GOLD 1-2 for %WA fifth to third and LA fifth to third and between GOLD 0 and GOLD 3-4 for all six parameters (p < 0.05); %WA fifth to third had the best cutoff value of 1.02 (sensitivity, 92%; specificity, 86%) for diagnosis of COPD (GOLD 1-4). The %WA fifth to first of 1.51 (sensitivity, 83%; specificity, 89%) was best for diagnosis of GOLD 3-4. CONCLUSION: Ratios of peripheral-to-central airway LA and %WA show improved correlation with COPD severity.

A highly efficient peptide substrate for EGFR activates the kinase by inducing aggregation.

Formation of an asymmetric dimer by the EGFR (epidermal growth factor receptor) kinase domains results in allosteric activation. Since this dimer does not readily form in solution, the EGFR kinase domain phosphorylates most peptide substrates with a relatively low catalytic efficiency. Peptide C is a synthetic peptide substrate of EGFR developed by others that is phosphorylated with a significantly higher catalytic efficiency, and we sought to understand the basis for this. Peptide C was found to increase EGFR kinase activity by promoting formation of the EGFR kinase domain asymmetric dimer. Activation of the kinase domain by Peptide C also enhances phosphorylation of other substrates. Aggregation of the EGFR kinase domain by Peptide C probably underlies activation, and Peptide C precipitates several other proteins. Peptide C was found to form fibrils independent of the presence of EGFR, and these fibrils may facilitate aggregation and activation of the kinase domain. These results establish that a peptide substrate of EGFR may increase catalytic activity by promoting kinase domain dimerization by an aggregation-mediated mechanism.

Radiologic feature of complications after artificial urinary sphincter implantation following total prostatectomy.

Incontinence following total prostatectomy for prostate cancer significantly impairs patient's quality of life. In severe cases, implantation of an artificial urinary sphincter (AUS) has shown favorable outcomes, enhancing continence by constricting the bulbous urethra. The AUS system consists of a pressure-maintaining balloon, control pump serving as the operational switch, cuff that constricts the urethra, and tubes and connectors that link these components, maintaining a continuous circuit through an internal pressure medium. Most instances of AUS dysfunction are attributed to circuit leaks leading to a reduction in internal pressure, which is identifiable on imaging by fluid accumulation around the circuit, balloon collapse, control pump deformation, and air within the circuit. When the AUS circuit is uncompromised, dysfunction may arise from issues such as the inability to compress the pump due to pain or displacement outside the scrotum or urinary tract obstruction caused by bladder hemorrhage/hematoma. Imaging plays a pivotal role in the evaluation of urinary tract injuries, hematomas/seromas, and infections associated with AUS placement or replacement. Understanding the function of AUS and its appearance on CT imaging is essential for accurately assessing AUS dysfunction and post-implantation complications, guiding clinical decision-making and improving patient care outcomes.

Computed tomography-based radiomic analysis for predicting pathological response and prognosis after neoadjuvant chemotherapy in patients with locally advanced esophageal cancer.

PURPOSE: Accurate prediction of prognosis and pathological response to neoadjuvant chemotherapy (NAC) is crucial for optimizing treatment strategies for patients with locally advanced esophageal cancer (LA-EC). This study aimed to investigate the use of radiomics for pretreatment CT in predicting the pathological response of patients with LA-EC to NAC. METHODS: Overall, 144 patients (145 lesions) with LA-EC who underwent pretreatment contrast-enhanced CT and then received NAC followed by surgery with pathological tumor regression grade (TRG) analysis were enrolled. The obtained dataset was randomly divided into training and validation cohorts using fivefold cross-validation. CT-based radiomic features were extracted followed by the feature selection process using the variance threshold, SelectKBest, and least absolute shrinkage and selection operator methods. The radiomic model was constructed using six machine learning classifiers, and predictive performance was evaluated using ROC curve analysis in the training and validation cohorts. RESULTS: All patients were divided into responders (n = 40, 28%) and non-responders (n = 104, 72%) based on the TRG results and a statistically significant split by overall survival analysis (0.899 [0.754-0.961] vs. 0.630 [0.510-0.729], respectively). There were no significant differences between responders and non-responders in terms of age, sex, tumor size, tumor location, or histopathology. The mean AUC of fivefold in the validation cohort was 0.720 (confidence interval [CI]: 0.594-0.982), and the best AUC of the radiomic model using logistic regression to predict the non-responders was 0.815 (CI: 0.626-1.000, sensitivity 0.620, specificity 0.860). CONCLUSION: A radiomic model derived from contrast-enhanced CT may help stratify chemotherapy effect prediction and improve clinical decision-making.

Computed tomography findings of hepatobiliary systems in patients with immune checkpoint inhibitor-induced liver injury.

PURPOSE: The incidence of immune checkpoint inhibitor (ICI)-induced liver injury has increased recently; however, its imaging characteristics remain unclear. This study aimed to characterize the computed tomography (CT) findings of ICI-induced liver injury. METHODS: This was a single-center retrospective study of patients with ICI-induced liver injury who underwent CT between January 2020 and December 2021. Two board-certified radiologists independently evaluated the CT findings of the patients before the start of ICI therapy (pre-CT) and at the onset of ICI-induced liver injury (post-CT) to determine the presence or absence of imaging findings suggestive of hepatitis and cholangitis. ICI-induced liver injury was classified into three categories based on the CT findings: hepatitis alone, cholangitis alone, and overlapped (cholangitis plus hepatitis). RESULTS: A total of 19 patients were included in this study. Bile duct dilatation, bile duct wall thickening, non-edematous gallbladder wall thickening, hepatomegaly, periportal edema, and gallbladder wall edema were observed in the post-CT images of 12 (63.2%), 9 (60%), 11 (57.9%), 8 (42.1%), 6 (31.6%), and 2 (10.5%) patients, respectively. Wall thickening in the perihilar, distal, intrapancreatic bile duct and the cystic duct were observed in 53.3%, 60%, 46.7%, and 26.7% of the study population, respectively. Regarding the classification of ICI-induced liver injury, cholangitis alone was most common (36.8%), followed by overlapped (26.3%) and hepatitis alone (26.3%). CONCLUSIONS: Patients with ICI-induced liver injury demonstrated a higher incidence of biliary abnormalities than hepatic abnormalities on CT images; nonetheless, future studies with larger sample sizes are needed to validate these findings.

Quantitative evaluation of the reduction of distortion and metallic artifacts in magnetic resonance images using the multiacquisition variable­resonance image combination selective sequence.

Magnetic resonance imaging (MRI) is superior to computed tomography (CT) in determining changes in tissue structure, such as those observed following inflammation and infection. However, when metal implants or other metal objects are present, MRI exhibits more distortion and artifacts compared with CT, which hinders the accurate measurement of the implants. A limited number of reports have examined whether the novel MRI sequence, multiacquisition variable-resonance image combination selective (MAVRIC SL), can accurately measure metal implants without distortion. Therefore, the present study aimed to demonstrate whether MAVRIC SL could accurately measure metal implants without distortion and whether the area around the metal implants could be well delineated without artifacts. An agar phantom containing a titanium alloy lumbar implant was used for the present study and was imaged using a 3.0 T MRI machine. A total of three imaging sequences, namely MAVRIC SL, CUBE and magnetic image compilation (MAGiC), were applied and the results were compared. Distortion was evaluated by measuring the screw diameter and distance between the screws multiple times in the phase and frequency directions by two different investigators. The artifact region around the implant was examined using a quantitative method following standardization of the phantom signal values. It was revealed that MAVRIC SL was a superior sequence compared with CUBE and MAGiC, as there was significantly less distortion, a lack of bias between the two different investigators and significantly reduced artifact regions. These results suggested the possibility of utilizing MAVRIC SL for follow-up to observe metal implant insertions.

Risk factors for early death in transient myeloproliferative disorder without phenotypic features of Down syndrome: a case report and literature review.

Not only in newborns with Down syndrome, but newborns without phenotypic features of Down syndrome also develop transient myeloproliferative disorder (TMD). In these cases, trisomy 21 and related chromosomal abnormalities are either constitutionally mosaic or limited to blood cells. Risk factors for early death of these patients are unknown so far. We here report a fatal case of TMD without phenotypic features of Down syndrome and review literature to identify risk factors associated with early death. Not only are gestational age and white blood cell count risk factors for early death in TMD with Down syndrome, but they also appear to be risk factors in TMD without Down syndrome.

Pulmonary lymphatic drainage to the mediastinum based on computed tomographic observations of the primary complex of pulmonary histoplasmosis.

BACKGROUND: In the primary infection of pulmonary histoplasmosis, pulmonary lesions are commonly solitary and associated with hilar and/or mediastinal nodal diseases, which spontaneously resolve, resulting in calcifications in individuals with normal cellular immunity. PURPOSE: To assess the lymphatic drainage to the mediastinum from each pulmonary segment and lobe using computed tomographic (CT) observations of a calcified primary complex pulmonary histoplasmosis and predict which patients with N2 disease that would benefit from surgery. MATERIAL AND METHODS: We collected 585 CT studies of patients with primary complex histoplasmosis consisting of solitary calcified pulmonary lesions and calcified hilar and/or mediastinal nodal disease. Using the N stage criteria of non-small cell lung cancer, we assessed the distribution of the involved hilar and mediastinal nodes depending on the pulmonary segment of the lesion, with a focus on skip involvement. We also assessed the correlation between the incidence of N1 and skip N2 involvement and the mean number of involved mediastinal nodal stations in the non-skip N2 and skip N2 groups. RESULTS: Skip involvement was common in the apical segment (9/45, 20.0%), posterior segment (7/31, 22.6%), and mediolbasal segment (13/20, 65.0%) in the right lung, and in the apicoposterior segment (7/55, 12.7%), lateral basal segment (6/26, 23.1%), and posterobasal segment (16/47, 34.0%) in the left lung. The incidence of skip involvement in each segment showed a significant inverse correlation with that of N1 involvement (r = -0.51, P <0.05) in both lungs. The mean number of involved mediastinal nodal stations in the non-skip N2 and skip N2 groups in all segments of both lungs were 1.4 (434/301) and 1.2 (93/77), and the former was significantly greater than the latter (P <0.01). CONCLUSION: Our data showed a predictable pattern of segmental and lobar lymphatic drainage to the mediastinum and suggested that skip involvement could represent the initial mediastinal node involvement via direct lymphatic drainage.

Methotrexate-Associated Lymphoproliferative Disorders Mimicking Granulomatosis With Polyangiitis: A Radiological Diagnostic Challenge.

Methotrexate-associated lymphoproliferative disorders (MTX-LPD) frequently involve the extranodal organs throughout the body. Among the extranodal occurrences of MTX-LPD, pulmonary involvement is most frequent. In contrast, there are only a few reports of MTX-LPD in the nasal cavity or paranasal sinuses. Moreover, there are no previous reports of MTX-LPD mimicking granulomatosis with polyangiitis (GPA) in imaging examinations. We describe a case of a 53-year-old woman with MTX-LPD mimicking GPA in the nasal cavity and lungs. She complained of left nasal obstruction and discharge, general fatigue, and continual fever for 2 months. The patient had been diagnosed with rheumatoid arthritis and received methotrexate (MTX) for over 10 years. Contrast-enhanced computed tomography revealed unenhanced masses in the nasal cavity and multiple masses with cavitary changes in the bilateral lungs, suggesting GPA. However, histological examination of the nasal lesion and a history of MTX treatment indicated a diffuse large B-cell lymphoma type MTX-LPD. Two weeks after MTX withdrawal, prominent improvements in both lesions were observed. Complete regression of the nasal lesion was observed 3 months after discontinuation of MTX. Thus, MTX-LPD may mimic GPA in imaging examinations.

Erratum: Exploring APOBEC3A and APOBEC3B substrate specificity and their role in HPV positive head and neck cancer.

[This corrects the article DOI: 10.1016/j.isci.2022.105077.].

Automatic breast carcinoma detection in histopathological micrographs based on Single Shot Multibox Detector.

Background: A diagnosis with histological classification by pathologists is very important for appropriate treatments to improve the prognosis of patients with breast cancer. However, the number of pathologists is limited, and assisting the pathological diagnosis by artificial intelligence becomes very important. Here, we presented an automatic breast lesions detection model using microscopic histopathological images based on a Single Shot Multibox Detector (SSD) for the first time and evaluated its significance in assisting the diagnosis. Methods: We built the data set and trained the SSD model with 1361 microscopic images and evaluated using 315 images. Pathologists and medical students diagnosed the images with or without the assistance of the model to investigate the significance of our model in assisting the diagnosis. Results: The model achieved 88.3% and 90.5% diagnostic accuracies in 3-class (benign, non-invasive carcinoma, or invasive carcinoma) or 2-class (benign or malignant) classification tasks, respectively, and the mean intersection over union was 0.59. Medical students achieved a remarkably higher diagnostic accuracy score (average 84.7%) with the assistance of the model compared to those without assistance (average 67.4%). Some people diagnosed images in a short time using the assistance of the model (shorten by average 6.4 min) while others required a longer time (extended by 7.2 min). Conclusion: We presented the automatic breast lesions detection method at high speed using histopathological micrographs. The present system may conveniently support the histological diagnosis by pathologists in laboratories.

Exploring ABOBEC3A and APOBEC3B substrate specificity and their role in HPV positive head and neck cancer.

APOBEC3 family members are cytidine deaminases catalyzing conversion of cytidine to uracil. Many studies have established a link between APOBEC3 expression and cancer development and progression, especially APOBEC3A (A3A) and APOBEC3B (A3B). Preclinical studies with human papillomavirus positive (HPV+) head and neck squamous cell carcinoma (HNSCC) and clinical trial specimens revealed induction of A3B, but not A3A expression after demethylation. We examined the kinetic features of the cytidine deaminase activity for full length A3B and found that longer substrates and a purine at -2 position favored by A3B, whereas A3A prefers shorter substrates and an adenine or thymine at -2 position. The importance and biological significance of A3B catalytic activity rather than A3A and a preference for purine at the -2 position was also established in HPV+ HNSCCs. Our study explored factors influencing formation of A3A and A3B-related cancer mutations that are essential for understanding APOBEC3-related carcinogenesis and facilitating drug discovery.

Effect of ageing and pulmonary inflammation on the incidence and number of cross-bridging structures in pneumothorax patients.

BACKGROUND: There is an improved prognosis for T4 non-small-cell lung cancer in patients who show particular patterns of direct mediastinal invasion. The particular patterns suggest the presence of direct pathways other than the pulmonary hilum between each of the lungs and the mediastinum/chest wall. PURPOSE: To determine the incidence and number of such direct pathways in pneumothorax patients as well as the factors that affect the development of these pathways. MATERIAL AND METHODS: Two radiologists independently analyzed multidetector computed tomographic images of 81 patients with pneumothorax to assess the incidence and distribution pattern of the cross-bridging structures in the pleural cavity. RESULTS: Cross-bridging structures were observed in the right pneumothorax in 34/54 (63%) patients and in the left pneumothorax in 19/32 (59%) patients. The number of cross-bridging structures was found to be positively correlated with ageing and pulmonary disease. The distribution patterns of cross-bridging structures were found to be specific in formation and often in repeated locations, regardless of the presence of pulmonary disease or the age of the patient. CONCLUSION: Cross-bridging structures in pneumothoraces were found more frequently in older patients and in patients with pulmonary disease. However, some of the cross-bridging structures may have been congenital because of their specific formations and repeated locations.