Refined scan protocol for the evaluation of pulmonary perfusion standardized image quality and reduced radiation dose in dynamic chest radiography.

PURPOSE: Dynamic chest radiography (DCR) is a novel imaging technique used to noninvasively evaluate pulmonary perfusion. However, the standard DCR protocol, which is roughly adapted to the patient's body size, occasionally causes over- or underexposure, which could influence clinical evaluation. Therefore, we proposed a refined protocol by increasing the number of patient body mass index (BMI) categories from three to seven groups and verified its usefulness by comparing the image sensitivity indicators (S-values) and entrance surface doses (ESDs) of the conventional protocol with those of our refined protocol. METHODS: This retrospective observational study included 388 datasets (standing position, 224; supine position, 164) for the conventional protocol (December 2019-April 2021) and 336 datasets (standing position, 233; supine position, 103) for the refined protocol (June-November 2021). The conventional protocol (BMI-3 protocol) divided the patients into three BMI groups (BMI < 17, 17≤BMI < 25, and BMI ≥ 25 kg/m2 ), whereas the refined protocol (BMI-7 protocol) divided the patients into seven BMI groups (BMI < 17, 17 ≤ BMI < 20, 20 ≤ BMI < 23, 23 ≤ BMI < 26, 26 ≤ BMI < 29, 29 ≤ BMI < 32, and BMI ≥ 32 kg/m2 ). The coefficients of variation (CVs) for the S-values and ESDs acquired using the two protocols were compared. RESULTS: The CVs of the S-values in the BMI-7 protocol group were significantly lower than those in the BMI-3 protocol group for the standing (28.8% vs. 16.7%; p < 0.01) and supine (24.5% vs. 17.7%; p < 0.01) positions. The ESDs of patients scanned using the BMI-7 protocol were significantly lower than those scanned using the BMI-3 protocol in the standing (1.3 vs. 1.1 mGy; p < 0.01) and supine positions (2.5 vs. 1.6 mGy; p < 0.01), although the mean BMI of the two groups were similar. CONCLUSION: We introduced the BMI-7 protocol and demonstrated its standardized image quality and reduced radiation exposure in patients undergoing DCR.

Efficacy of Dynamic Chest Radiography for Chronic Thromboembolic Pulmonary Hypertension.

Background While current guidelines require lung ventilation-perfusion (V/Q) scanning as the first step to diagnose chronic pulmonary embolism in pulmonary hypertension (PH), its use may be limited by low availability and/or exposure to ionizing radiation. Purpose To compare the performance of dynamic chest radiography (DCR) and lung V/Q scanning for detection of chronic thromboembolic PH (CTEPH). Materials and Methods Patients with PH who underwent DCR and V/Q scanning in the supine position from December 2019 to July 2021 were retrospectively screened. The diagnosis of CTEPH was confirmed with right heart catheterization and invasive pulmonary angiography. Observer tests were conducted to evaluate the diagnostic accuracy of DCR and V/Q scanning. The lungs were divided into six areas (upper, middle, and lower for both) in the anteroposterior image, and the number of lung areas with thromboembolic perfusion defects was scored. Diagnostic performance was compared between DCR and V/Q scanning using the area under the receiver operating characteristic curve. Agreement between the interpretation of DCR and that of V/Q scanning was assessed using the Cohen kappa coefficient and percent agreement. Results A total of 50 patients with PH were analyzed: 29 with CTEPH (mean age, 64 years ± 15 [SD]; 19 women) and 21 without CTEPH (mean age, 61 years ± 22; 14 women). The sensitivity, specificity, and accuracy of DCR were 97%, 86%, and 92%, respectively, and those of V/Q scanning were 100%, 86%, and 94%, respectively. Areas under the receiver operating characteristic curve for DCR and V/Q scanning were 0.92 (95% CI: 0.79, 0.97) and 0.93 (95% CI: 0.78, 0.98). Agreement between the consensus interpretation of DCR and that of V/Q scanning was substantial (κ = 0.79 [95% CI: 0.61, 0.96], percent agreement = 0.9 [95% CI: 0.79, 0.95]). Conclusion Dynamic chest radiography had similar efficacy to ventilation-perfusion scanning in the detection of chronic thromboembolic pulmonary hypertension. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Wandtke and Koproth-Joslin in this issue.

Prevalence and mortality associations of interstitial lung abnormalities in rheumatoid arthritis within a multicentre prospective cohort of smokers.

OBJECTIVE: To investigate the prevalence and mortality impact of interstitial lung abnormalities (ILAs) in RA and non-RA comparators. METHODS: We analysed associations between ILAs, RA, and mortality in COPDGene, a multicentre prospective cohort study of current and past smokers, excluding known interstitial lung disease (ILD) or bronchiectasis. All participants had research chest high-resolution CT (HRCT) reviewed by a sequential reading method to classify ILA as present, indeterminate or absent. RA cases were identified by self-report RA and DMARD use; non-RA comparators had neither an RA diagnosis nor used DMARDs. We examined the association and mortality risk of RA and ILA using multivariable logistic regression and Cox regression. RESULTS: We identified 83 RA cases and 8725 non-RA comparators with HRCT performed for research purposes. ILA prevalence was 16.9% in RA cases and 5.0% in non-RA comparators. After adjusting for potential confounders, including genetics, current/past smoking and other lifestyle factors, ILAs were more common among those with RA compared with non-RA [odds ratio 4.76 (95% CI 2.54, 8.92)]. RA with ILAs or indeterminate for ILAs was associated with higher all-cause mortality compared with non-RA without ILAs [hazard ratio (HR) 3.16 (95% CI 2.11, 4.74)] and RA cases without ILA [HR 3.02 (95% CI 1.36, 6.75)]. CONCLUSIONS: In this cohort of smokers, RA was associated with ILAs and this persisted after adjustment for current/past smoking and genetic/lifestyle risk factors. RA with ILAs in smokers had a 3-fold increased all-cause mortality, emphasizing the importance of further screening and treatment strategies for preclinical ILD in RA.

The Proteomic Profile of Interstitial Lung Abnormalities.

Rationale: Knowledge on biomarkers of interstitial lung disease is incomplete. Interstitial lung abnormalities (ILAs) are radiologic changes that may present in its early stages. Objectives: To uncover blood proteins associated with ILAs using large-scale proteomics methods. Methods: Data from two prospective cohort studies, the AGES-Reykjavik (Age, Gene/Environment Susceptibility-Reykjavik) study (N = 5,259) for biomarker discovery and the COPDGene (Genetic Epidemiology of COPD) study (N = 4,899) for replication, were used. Blood proteins were measured using DNA aptamers, targeting more than 4,700 protein analytes. The association of proteins with ILAs and ILA progression was assessed with regression modeling, as were associations with genetic risk factors. Adaptive Least Absolute Shrinkage and Selection Operator models were applied to bootstrap data samples to discover sets of proteins predictive of ILAs and their progression. Measurements and Main Results: Of 287 associations, SFTPB (surfactant protein B) (odds ratio [OR], 3.71 [95% confidence interval (CI), 3.20-4.30]; P = 4.28 × 10-67), SCGB3A1 (Secretoglobin family 3A member 1) (OR, 2.43 [95% CI, 2.13-2.77]; P = 8.01 × 10-40), and WFDC2 (WAP four-disulfide core domain protein 2) (OR, 2.42 [95% CI, 2.11-2.78]; P = 4.01 × 10-36) were most significantly associated with ILA in AGES-Reykjavik and were replicated in COPDGene. In AGES-Reykjavik, concentrations of SFTPB were associated with the rs35705950 MUC5B (mucin 5B) promoter polymorphism, and SFTPB and WFDC2 had the strongest associations with ILA progression. Multivariate models of ILAs in AGES-Reykjavik, ILAs in COPDGene, and ILA progression in AGES-Reykjavik had validated areas under the receiver operating characteristic curve of 0.880, 0.826, and 0.824, respectively. Conclusions: Novel, replicated associations of ILA, its progression, and genetic risk factors with numerous blood proteins are demonstrated as well as machine-learning-based models with favorable predictive potential. Several proteins are revealed as potential markers of early fibrotic lung disease.

Associations of Monocyte Count and Other Immune Cell Types with Interstitial Lung Abnormalities.

Rationale: Higher blood monocyte counts are associated with worse survival in adults with clinically diagnosed pulmonary fibrosis. Their association with the development and progression of interstitial lung abnormalities (ILA) in humans is unknown. Objectives: We evaluated the associations of blood monocyte count, and other immune cell types, with ILA, high-attenuation areas, and FVC in four independent cohorts. Methods: We included participants with measured monocyte counts and computed tomographic (CT) imaging enrolled in MESA (Multi-Ethnic Study of Atherosclerosis, n = 484), AGES-Reykjavik (Age/Gene Environment Susceptibility Study, n = 3,547), COPDGene (Genetic Epidemiology of COPD, n = 2,719), and the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points, n = 646). Measurements and Main Results: After adjustment for covariates, a 1-SD increment in blood monocyte count was associated with ILA in MESA (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.0-1.8), AGES-Reykjavik (OR, 1.2; 95% CI, 1.1-1.3), COPDGene (OR, 1.3; 95% CI, 1.2-1.4), and ECLIPSE (OR, 1.2; 95% CI, 1.0-1.4). A higher monocyte count was associated with ILA progression over 5 years in AGES-Reykjavik (OR, 1.2; 95% CI, 1.0-1.3). Compared with participants without ILA, there was a higher percentage of activated monocytes among those with ILA in MESA. Higher monocyte count was associated with greater high-attenuation areas in MESA and lower FVC in MESA and COPDGene. Associations of other immune cell types were less consistent. Conclusions: Higher blood monocyte counts were associated with the presence and progression of interstitial lung abnormalities and lower FVC.

Traction Bronchiectasis/Bronchiolectasis on CT Scans in Relationship to Clinical Outcomes and Mortality: The COPDGene Study.

Background The clinical impact of interstitial lung abnormalities (ILAs) on poor prognosis has been reported in many studies, but risk stratification in ILA will contribute to clinical practice. Purpose To investigate the association of traction bronchiectasis/bronchiolectasis index (TBI) with mortality and clinical outcomes in individuals with ILA by using the COPDGene cohort. Materials and Methods This study was a secondary analysis of prospectively collected data. Chest CT scans of participants with ILA for traction bronchiectasis/bronchiolectasis were evaluated and outcomes were compared with participants without ILA from the COPDGene study (January 2008 to June 2011). TBI was classified as follows: TBI-0, ILA without traction bronchiectasis/bronchiolectasis; TBI-1, ILA with bronchiolectasis but without bronchiectasis or architectural distortion; TBI-2, ILA with mild to moderate traction bronchiectasis; and TBI-3, ILA with severe traction bronchiectasis and/or honeycombing. Clinical outcomes and overall survival were compared among the TBI groups and the non-ILA group by using multivariable linear regression model and Cox proportional hazards model, respectively. Results Overall, 5295 participants (median age, 59 years; IQR, 52-66 years; 2779 men) were included, and 582 participants with ILA and 4713 participants without ILA were identified. TBI groups were associated with poorer clinical outcomes such as quality of life scores in the multivariable linear regression model (TBI-0: coefficient, 3.2 [95% CI: 0.6, 5.7; P = .01]; TBI-1: coefficient, 3.3 [95% CI: 1.1, 5.6; P = .003]; TBI-2: coefficient, 7.6 [95% CI: 4.0, 11; P < .001]; TBI-3: coefficient, 32 [95% CI: 17, 48; P < .001]). The multivariable Cox model demonstrated that ILA without traction bronchiectasis (TBI-0-1) and with traction bronchiectasis (TBI-2-3) were associated with shorter overall survival (TBI-0-1: hazard ratio [HR], 1.4 [95% CI: 1.0, 1.9; P = .049]; TBI-2-3: HR, 3.8 [95% CI: 2.6, 5.6; P < .001]). Conclusion Traction bronchiectasis/bronchiolectasis was associated with poorer clinical outcomes compared with the group without interstitial lung abnormalities; TBI-2 and 3 were associated with shorter survival. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Lee and Im in this issue.

Interstitial Lung Abnormalities at CT: Subtypes, Clinical Significance, and Associations with Lung Cancer.

Interstitial lung abnormality (ILA) is defined as an interstitial change detected incidentally on CT images. It is seen in 4%-9% of smokers and 2%-7% of nonsmokers. ILA has a tendency to progress with time and is associated with respiratory symptoms, decreased exercise capability, reduced pulmonary function, and increased mortality. ILAs can be classified into three subcategories: nonsubpleural, subpleural nonfibrotic, and subpleural fibrotic. In cases of ILA, clinically significant interstitial lung disease should be identified and requires clinically driven management by a pulmonologist. Risk factors for the progression of ILA include clinical elements (ie, inhalation exposures, medication use, radiation therapy, thoracic surgery, physiologic findings, and gas exchange findings) and radiologic elements (ie, basal and peripheral predominance and fibrotic findings). It is recommended that individuals with one or more clinical or radiologic risk factors for progression of ILA be actively monitored with pulmonary function testing and CT. To avoid overcalling ILA at CT, radiologists must recognize the imaging pitfalls, including centrilobular nodularity, dependent abnormality, suboptimal inspiration, osteophyte-related lesions, apical cap and pleuroparenchymal fibroelastosis-like lesions, aspiration, and infection. There is a close association between ILA and lung cancer, and many studies have reported an increased incidence of lung cancer, worse prognoses, and/or increased pulmonary complications in relation to cancer treatment in patients with ILA. ILA is considered to be an important comorbidity in patients with lung cancer. Accordingly, all radiologists involved with body CT must have sound knowledge of ILAs owing to the high prevalence and potential clinical significance of these anomalies. An overview of ILAs, including a literature review of the associations between ILAs and lung cancer, is presented. ©RSNA, 2022.

Right Ventricular Extracellular Volume with Dual-Layer Spectral Detector CT: Value in Chronic Thromboembolic Pulmonary Hypertension.

Background Right ventricular (RV) extracellular volumes (ECVs), as a surrogate for histologic fibrosis, have not been sufficiently investigated. Purpose To evaluate and compare RV and left ventricular (LV) ECVs obtained with dual-layer spectral detector CT (DLCT) in chronic thromboembolic pulmonary hypertension (CTEPH) and investigate the clinical importance of RV ECV. Materials and Methods Retrospective analysis was performed on data from 31 patients with CTEPH (17 were not treated with pulmonary endarterectomy [PEA] or balloon pulmonary angioplasty [BPA] and 14 were) and eight control subjects who underwent myocardial delayed enhancement (MDE) DLCT from January 2019 to June 2020. The ECVs in the RV and LV walls were calculated by using iodine density as derived from spectral data pertaining to MDE. Statistical analyses were performed with one-way repeated analysis of variance with the Tukey post hoc test or the Kruskal-Wallis test with the Steel-Dwass test and linear regression analysis. Results The PEA- and BPA-naive group showed significantly higher ECVs than the PEA- or BPA-treated group and control group in the septum (28.2% ± 2.9 vs 24.3% ± 3.6, P = .005), anterior right ventricular insertion point (RVIP) (32.9% ± 4.6 vs 25.3% ± 3.6, P < .001), posterior RVIP (35.2% ± 5.2 vs 27.3% ± 4.2, P < .001), mean RVIP (34.0% ± 4.2 vs 26.3% ± 3.4, P < .001), RV free wall (29.5% ± 3.3 vs 25.9% ± 4.1, P = .036), and mean RV wall (29.1% ± 3.0 vs 26.1% ± 3.1, P = .029). There were no significant differences between the PEA- or BPA-treated group and control subjects in these segments (septum, P = .93; anterior RVIP, P = .38; posterior RVIP, P = .52; mean RVIP, P = .36; RV free wall, P = .97; and mean RV, P = .33). There were significant correlations between ECV and mean pulmonary artery pressure (PAP) or brain natriuretic peptide (BNP) in the mean RVIP (mean PAP: R = 0.66, P < .001; BNP: R = 0.44, P = .014) and the mean RV (mean PAP: R = 0.49, P = .005; BNP: R = 0.44, P = .013). Conclusion Right ventricular and right ventricular insertion point extracellular volumes could be noninvasive surrogate markers of disease severity and reverse tissue remodeling in chronic thromboembolic pulmonary hypertension. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Sandfort and Bluemke in this issue.

Characterization of parotid gland tumors: added value of permeability MR imaging to DWI and DCE-MRI.

OBJECTIVES: To determine added value of permeability MRI in parotid tumor characterization to T2-weighted imaging (T2WI), semi-quantitative analysis of time-intensity curve (TIC), and intra-voxel incoherent motion diffusion-weighted imaging (IVIM-DWI). METHODS: This retrospective study was approved by the institutional review board, and the informed consent was waived. Sixty-one parotid tumors in 61 patients were examined using T2WI, IVIM-DWI, and permeability MRI. TIC patterns were categorized as persistent, washout, or plateau. Signal intensity ratio of lesion-to-muscle on T2WI, apparent diffusion coefficients (ADCs), D and f values from IVIM-DWI, and Ktrans, kep, Ve, and Vp values from permeability MRI were measured. Multiple comparisons were applied to determine whether any differences among 4 histopathologic types (pleomorphic adenomas, Warthin's tumors, other benign tumors, and malignant tumors) existed. Diagnostic accuracy was compared before and after modification diagnosis referring to permeability MRI. In a validation study, 60 parotid tumors in 60 patients were examined. RESULTS: ADC and D values of malignant tumors were significantly lower than those of benign tumors other than Warthin's tumors, but higher than those of Warthin's tumors. kep and Vp values of Warthin's tumors were significantly higher than those of malignant tumors. Multivariate analyses showed that TIC pattern, D, and kep values were suitable parameters. McNemar's test showed a significant increase of sensitivity (11/12, 92%) and specificity (46/49, 94%) with adding kep. The validation study yielded high sensitivity (14/16, 88%) and specificity (41/44, 93%). CONCLUSION: Permeability MRI offers added value to IVIM-MRI and semi-quantitative TIC analysis of DCE-MRI in characterization of parotid tumors KEY POINTS: • Permeability MR imaging offers added value in the characterization of parotid gland tumors in combination with semi-quantitative TIC analysis and IVIM analyses with D parameter. • The combination of TIC pattern, D, and kep might facilitate accurate characterization of parotid gland tumor, thereby avoiding unnecessary surgery for benign tumors or delayed treatment for malignant tumors. • A combination of permeability and diffusion MR imaging can be used to guide the selection of an appropriate biopsy site.

Imaging Patterns Are Associated with Interstitial Lung Abnormality Progression and Mortality.

Rationale: Interstitial lung abnormalities (ILA) are radiologic abnormalities on chest computed tomography scans that have been associated with an early or mild form of pulmonary fibrosis. Although ILA have been associated with radiologic progression, it is not known if specific imaging patterns are associated with progression or risk of mortality. Objectives: To determine the role of imaging patterns on the risk of death and ILA progression. Methods: ILA (and imaging pattern) were assessed in 5,320 participants from the AGES-Reykjavik Study, and ILA progression was assessed in 3,167 participants. Multivariable logistic regression was used to assess factors associated with ILA progression, and Cox proportional hazards models were used to assess time to mortality. Measurements and Main Results: Over 5 years, 327 (10%) had ILA on at least one computed tomography, and 1,435 (45%) did not have ILA on either computed tomography. Of those with ILA, 238 (73%) had imaging progression, whereas 89 (27%) had stable to improved imaging; increasing age and copies of MUC5B genotype were associated with imaging progression. The definite fibrosis pattern was associated with the highest risk of progression (odds ratio, 8.4; 95% confidence interval, 2.7-25; P = 0.0003). Specific imaging patterns were also associated with an increased risk of death. After adjustment, both a probable usual interstitial pneumonia and usual interstitial pneumonia pattern were associated with an increased risk of death when compared with those indeterminate for usual interstitial pneumonia (hazard ratio, 1.7; 95% confidence interval, 1.2-2.4; P = 0.001; hazard ratio, 3.9; 95% confidence interval, 2.3-6.8;P < 0.0001), respectively. Conclusions: In those with ILA, imaging patterns can be used to help predict who is at the greatest risk of progression and early death.

Amide proton transfer imaging to predict tumor response to neoadjuvant chemotherapy in locally advanced rectal cancer.

BACKGROUND AND AIM: The amount of proteins and peptides can be estimated with amide proton transfer (APT) imaging. Previous studies demonstrated the usefulness of APT imaging to predict tumor malignancy. We determined whether APT imaging can predict the tumor response to neoadjuvant chemotherapy (NAC) in patients with locally advanced rectal cancer (LARC). METHODS: Seventeen patients with LARC who underwent a pretherapeutic magnetic resonance examination including APT imaging and NAC (at least two courses) were enrolled. The APT-weighted imaging (WI) signal intensity (SI) (%) was defined as magnetization transfer ratio asymmetry (MTRasym ) at the offset of 3.5 ppm. Each tumor was histologically evaluated for the degree of degeneration and necrosis and then classified as one of five histological Grades (0, none; 1a, less than 1/3; 1b, 1/3 to 2/3; 2, more than 2/3; 3, all). We compared the mean APTWI SIs of the tumors between the Grade 0/1a/1b (low-response group) and Grade 2/3 (high-response group) by Student's t-test. We used receiver operating characteristics curves to determine the diagnostic performance of the APTWI SI for predicting the tumor response. RESULTS: The mean APTWI SI of the low-response group (n = 12; 3.05 ± 1.61%) was significantly higher than that of the high-response group (n = 5; 1.14 ± 1.13%) (P = 0.029). The area under the curve for predicting the tumor response using the APTWI SI was 0.87. When ≥2.75% was used as an indicator of low-response status, 75% sensitivity and 100% specificity of the APTWI SI were obtained. CONCLUSION: Pretherapeutic APT imaging can predict the tumor response to NAC in patients with LARC.

Amide Proton Transfer MR Imaging of Endometrioid Endometrial Adenocarcinoma: Association with Histologic Grade.

Purpose To evaluate the utility of amide proton transfer (APT) imaging in estimating histologic grades of endometrioid endometrial adenocarcinoma (EEA). Materials and Methods The institutional review board approved this prospective study. Between June 2012 and March 2016, 32 patients with EEA underwent magnetic resonance (MR) imaging. After their surgical procedures, their EEAs were confirmed pathologically and classified into histologic grades: grade 1 (n = 11), grade 2 (n = 11), and grade 3 (n = 10). The APT signal intensities (SIs) and the mean and minimum apparent diffusion coefficients (ADCs) of the three grades were calculated and compared. Spearman rank correlation coefficient was also calculated between the APT SIs and histologic grades, and between the ADCs and histologic grades. Results The Spearman correlation coefficient with histologic grade of the APT SIs, the mean ADC, and the minimum ADC were 0.55 (P = .001), 0.03 (P = .84), and -0.30 (P = .09), respectively. The average APT SIs and the mean and minimum ADCs were 2.2% ± 0.2 (standard deviation), 0.9 × 10-3 mm2/sec ± 0.2, and 0.6 × 10-3 mm2/sec ± 0.1 for grade 1; 3.2% ± 0.3, 0.8 × 10-3 mm2/sec ± 0.1, and 0.5 × 10-3 mm2/sec ± 0.1 for grade 2; and 3.7% ± 0.3, 0.9 × 10-3 mm2/sec ± 0.1, and 0.5 × 10-3 mm2/sec ± 0.1 for grade 3, respectively. The APT SIs of grade 3 EEA were significantly higher than those of grade 1 EEA (P = .01), but other pairwise comparisons did not reveal any significant differences (P = .06-.51). The mean and minimum ADCs showed no significant differences among the three histologic grades (P =.13-.51). Conclusion The APT SI was positively correlated with the histologic grades of EEA. © RSNA, 2017 Online supplemental material is available for this article.

Spalt-like transcription factor 4 immunopositivity is associated with epithelial cell adhesion molecule expression in combined hepatocellular carcinoma and cholangiocarcinoma.

AIM: Combined hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) (cHCC-CC) is a rare biphasic liver cancer. Recent studies have demonstrated that cHCC-CC originates from hepatic progenitor cells (HPCs). Spalt-like transcription factor 4 (SALL4) is a marker for a progenitor subclass of HCC with an aggressive phenotype. However, little has been revealed about SALL4 expression in cHCC-CC. The aims of this study were to report SALL4 immunopositivity and the results of clinicopathological analysis in cHCC-CC, and to examine the two different nuclear immunostaining patterns for SALL4. METHODS AND RESULTS: We defined the diffuse finely granular nuclear immunostaining pattern as immunopositive for SALL4; this was observed in eight (8.9%) of 90 cHCC-CCs. SALL4 immunopositivity was significantly associated with immunopositivity for α-fetoprotein, glypican 3, and epithelial cell adhesion molecule (EpCAM). There was no relationship between SALL4 immunopositivity and prognosis. We confirmed SALL4 mRNA expression in samples with a punctuate/clumped immunostaining pattern, which showed a significantly lower rate of immunopositivity for EpCAM than those with a diffuse finely granular pattern. CONCLUSIONS: SALL4 immunopositivity is not a prognostic factor in cHCC-CC; however, it is associated with α-fetoprotein, glypican 3 and EpCAM immunopositivity, indicating the mechanism of carcinogenesis. Further study is necessary to interpret the immunostaining pattern for SALL4.

BAP1 immunohistochemistry and p16 FISH results in combination provide higher confidence in malignant pleural mesothelioma diagnosis: ROC analysis of the two tests.

Differentiation of malignant pleural mesothelioma (MPM) from benign mesothelial proliferation remains problematic. Loss of nuclear staining of BRCA1-associated protein 1 (BAP1; detected using immunohistochemistry (IHC)) and homozygous deletion (HD) of p16 (detected using fluorescence in situ hybridization (FISH)) are useful for differentiation of MPM from reactive mesothelial hyperplasia (RMH), but the correlation between BAP1 expression loss and p16 HD has not been fully described. We performed BAP1 IHC and p16-specific FISH for 40 MPM and 20 RMH cases, and measured proportions of cells showing BAP1 expression and p16 HD for each case. The diagnostic accuracy for MPM and the cut-off values of the two methods were assessed using receiver operating characteristic (ROC) analysis. BAP1 expression loss, p16 HD and coexistence of both were present in 27 (67.5 %), 27 (67.5 %) and 17 (42.5 %) MPM cases, respectively. Three MPM cases (7.5 %) and all 20 RMH cases had neither BAP1 loss nor p16 HD. There was no correlation between the results of the two methods. Their combination showed higher sensitivity (92.5 %, 37/40) and estimated probability than BAP1 IHC and p16-specific FISH used alone. BAP1 IHC and p16-specific FISH have independent diagnostic value, and have increased reliability when used in combination, for MPM diagnosis.

Deletion status of p16 in effusion smear preparation correlates with that of underlying malignant pleural mesothelioma tissue.

Differentiating malignant pleural mesothelioma (MPM) cells morphologically from reactive mesothelial hyperplasia cells is problematic. Homozygous deletion (HD) of p16 (CDKN2A), detected by FISH, is a good marker of malignancy and is useful to differentiate between these cells. However, the correlation between the p16 status of effusion smears and that of the underlying MPM tissues has not been investigated. We used p16-specific FISH to investigate 20 cases of MPM from which both effusion cytologic smears and histologic specimens were available. In five cases, histologic specimens included both an invasive component and surface mesothelial proliferation. In 14 cases (70%), MPM cells in both tissue sections and effusion smears were p16 HD-positive. Conversely, MPM cells in the remaining six tumors (30%) were p16 HD-negative in both tissue sections and effusion smears. For all five MPM cases with surface mesothelial proliferations and invasive components, the effusion smears, surface mesothelial proliferations, and invasive MPM components all displayed p16 deletion. Moreover, the extent to which p16 was deleted in smears highly correlated with the extent of p16 deletion in tissues. The p16 deletion percentages were also similar among smears, tissue surface proliferations, and invasive components. In cases with clinical and radiologic evidence of a diffuse pleural tumor, detection of p16 deletion in cytologic smear samples may permit MPM diagnosis without additional tissue examination. However, the absence of p16 deletion in cytologic smear samples does not preclude MPM.

Diffuse intrapulmonary malignant mesothelioma presenting with miliary pulmonary nodules: A case report.

A 67-year-old male with a history of asbestos exposure presented with fever, cough, and dyspnea and was found to have diffuse granular shadowing in both lungs, right pleural effusion, and hilar and mediastinal lymphadenopathy upon chest computed tomography. For definitive diagnosis, a thoracoscopic lung biopsy was performed. Intraoperative findings showed no remarkable macroscopic changes in the visceral and parietal pleura, although a high level of hyaluronic acid in the pleural effusion was noted. Histological findings showed proliferation of atypical cells with round-to-oval nuclei, prominent nucleoli, and eosinophilic cytoplasms. These cells were arranged into sheets or tubules and were located predominantly in the lung parenchyma. Lymphovascular invasion was conspicuous. Immunohistochemically, tumor cells were positive for calretinin, D2-40, and CK5/6, focally positive for Ber-EP4, but negative for WT-1, TTF-1, CEA, and MOC31. Fluorescence in situ hybridization for the tumor suppressor p16 revealed homozygous deletion in the tumor cells. Therefore, we diagnosed the tumor as diffuse intrapulmonary malignant mesothelioma (DIMM). The patient had a poor response to chemotherapy and died 1 year after diagnosis. Although rare, DIMM should be considered when patients present with multiple, tiny intrapulmonary nodules, regardless of macroscopic pleural changes. Furthermore, this is the first report on p16 status in DIMM.

Surgical diagnosis and treatment of a solitary lung nodule of IgG4-related disease, mimicking primary lung carcinoma or metastatic lung tumour: A rare case.

INTRODUCTION: IgG4-related disease is a poorly understood immune disorder. Its features include tumour-like swelling of involved organs, lymphoplasmacytic infiltrate with IgG4 positive plasma cells. IgG4-related lung disease can manifest radiologically as various types of pulmonary abnormalities, including mass-like lesions and pleural effusion, and it may mimic malignant disease. PRESENTATION OF CASE: A 76-year-old man was found to have a 4-mm ground glass opacity in the left lower lobe of the lung on follow-up chest CT after surgery for colon carcinoma. This lesion gradually became consolidated and enlarged to 9 mm over about three years. We performed a video-assisted left basal segmentectomy for the purposes of both diagnosis and treatment. Pathological examination revealed lymphoplasmacytic infiltration, mainly with IgG4-positive plasma cells. DISCUSSION: A major characteristic of IgG4-related lung disease is multiple, small, bilateral, lung nodules and solid nodules reportedly being detected in almost all patients. However, solitary nodules are rare, being present in only 14 %. Moreover, this case shows extremely rare radiological findings in which a ground-glass opacity had gradually morphed into a solid nodule. It is difficult to differentiate IgG4-related lung nodules from other lung diseases, such as primary or metastatic lung tumours, standard interstitial pneumonia, organizing pneumonia. CONCLUSION: We have here presented a rare case of IgG4-related lung disease with a 3-year course, including detailed radiological findings. Surgery is very useful for both diagnosis and treatment of a small, solitary, deeply located, pulmonary nodule of IgG4-related lung disease.

Impact of a new deep-learning-based reconstruction algorithm on image quality in ultra-high-resolution CT: clinical observational and phantom studies.

OBJECTIVES: To demonstrate the effect of an improved deep learning-based reconstruction (DLR) algorithm on Ultra-High-Resolution Computed Tomography (U-HRCT) scanners. METHODS: Clinical and phantom studies were conducted. Thirty patients who underwent contrast-enhanced CT examination during the follow-up period were enrolled. Images were reconstructed using improved DLR [termed, New DLR, i.e., Advanced Intelligent Clear-IQ Engine (AiCE) Body Sharp] and conventional DLR (Conv DLR, AiCE Body) algorithms. Two radiologists assessed the overall image quality using a 5-point scale (5 = excellent; 1 = unacceptable). The noise power spectra (NPSs) were calculated to assess the frequency characteristics of the image noise, and the square root of area under the curve (√AUC NPS) between 0.05 and 0.50 cycle/mm was calculated as an indicator of the image noise. Dunnett's test was used for statistical analysis of the visual evaluation score, with statistical significance set at p < 0.05. RESULTS: The overall image quality of New DLR was better than that of the Conv DLR (4.2 ± 0.4 and 3.3 ± 0.4, respectively; p < 0.0001). All New DLR images had an overall image quality score above the average or excellent. The √AUCNPS value of New DLR was lower than that of Conv DLR (13.8 and 14.2, respectively). The median values of reconstruction time required with New DLR and Conv DLR were 5.0 and 7.8 min, respectively. CONCLUSIONS: The new DLR algorithm improved the image quality within a practical reconstruction time. ADVANCES IN KNOWLEDGE: The new DLR enables us to choose whether to improve image quality or reduce the dose.