Metastatic Pulmonary Calcification: Single-Center Review of Typical and Atypical Imaging Features.

PURPOSE: The purpose of this study is to bring attention to an atypical form of metastatic pulmonary calcification, which is conventionally described as a metabolic process with upper lobe predominance in patients with a specific clinical history, which has not been reported as a distinct entity. METHODS: Patients with metastatic pulmonary calcification (MPC) were first identified with mPower keyword search, including MPC or metastatic calcifications on computed tomography chest radiological reports. Patients were then filtered on likelihood of MPC based off imaging reports. Images were then reviewed by three senior radiologists for pertinent characteristics such as location of MPC, degree of calcifications and pleural effusions. Based on the predominant location of MPC, cases were labeled as either typical or atypical. Clinical and imaging characteristics relevant to MPC were noted and compared across typical and atypical cases. RESULTS: In our study, we describe 25 patients with MPC, 13 defined as typical MPC and 12 with atypical MPC. Through consensus of senior radiologists, MPC was deemed to be mild (52%), moderate (44%), or severe (4%). Twenty-three patients (92%) had underlying renal disease including 21 requiring dialysis at the time of diagnosis. Outside of age at diagnosis, there was no significant clinical difference between the two groups. Evaluation of imaging characteristics (average HU attenuation, 267; range, 186-295), pattern and distribution of calcification, and clinical history strongly supported a diagnosis of atypical MPC. CONCLUSION: This study presents several cases of lower lobe subpleural MPC associated with pleural effusions, which has not been reported as a distinct entity, despite comprising a significant portion of MPC cases at our institution.

Lung-Reporting and Data System 2.0: Impact of the Updated Approach to Juxtapleural Nodules During Lung Cancer Screening Using the National Lung Cancer Screening Trial Data Set.

PURPOSE: To determine the frequency of malignancy of nonperifissural juxtapleural nodules (JPNs) measuring 6 to < 10 mm in a subset of low-dose chest computed tomographies from the National Lung Cancer Screening Trial and the rate of down-classification of such nodules in Lung-Reporting and Data System (RADS) 2.0 compared with Lung-RADS 1.1. MATERIALS AND METHODS: A secondary analysis of a subset of the National Lung Screening Trial was performed. An exemption was granted by the Institutional Review Board. The dominant noncalcified nodule measuring 6 to <10 mm was identified on all available prevalence computed tomographies. Nodules were categorized as pleural or nonpleural. Benign or malignant morphology was recorded. Initial and updated categories based on Lung-RADS 1.1 and Lung-RADS 2.0 were assigned, respectively. The impact of the down-classification of JPN was assessed. Both classification schemes were compared using the McNemar test (P < 0.01). RESULTS: A total of 2813 patients (62 ± 5 y, 1717 men) with 4408 noncalcified nodules were studied. One thousand seventy-three dominant nodules measuring 6 to <10 mm were identified. Three hundred forty-eight (32.4%) were JPN. The updated scheme allowed down-classification of 310 JPN from categories 3 (n = 198) and 4A (n = 112) to category 2. We, therefore, estimate a 4.8% rate of down-classification to category 2 in the entire National Lung Screening Trial screening group. Two/348 (0.57%) JPN were malignant, both nonbenign in morphology. The false-positive rate decreased in the updated classification (P < 0.01). CONCLUSION: This study demonstrates the low malignant potential of benign morphology JPN measuring 6 mm to <10 mm. The Lung-RADS 2.0 approach to JPN is estimated to reduce short-term follow-ups and false-positive results.

Lung-RADS Version 1.0 versus Lung-RADS Version 1.1: Comparison of Categories Using Nodules from the National Lung Screening Trial.

Background The American College of Radiology updated Lung Imaging Reporting and Data System (Lung-RADS) version 1.0 to version 1.1 in May 2019, with the two key changes involving perifissural nodules (PFNs) and ground-glass nodules (GGNs) now designated as a negative screening result. This study examines the effects of these changes using National Lung Screening Trial (NLST) data. Purpose To determine the frequency of PFNs and GGNs reclassified from category 3 or 4A to the more benign category 2 in the updated Lung-RADS version 1.1, as compared with Lung-RADS version 1.0, using CT scans from the NLST. Materials and Methods In this secondary analysis of the NLST, the authors studied all noncalcified nodules (NCNs) found on the incident scan. Nodules were evaluated using criteria from both Lung-RADS version 1.0 and version 1.1, which were compared to determine changes in the number of nodules deemed benign. A McNemar test was used to assess statistical significance. Results A total of 2813 patients (mean age ± standard deviation, 62 years ± 5; 1717 men) with 4408 NCNs were studied. Of the largest 1092 solid NCNs measuring at least 6 mm but less than 10 mm, 216 (19.8%) were deemed PFNs (category 2) using Lung-RADS version 1.1. Eleven of the 1092 solid NCNs (1.0%) were malignant, but none were PFNs. Of 161 GGNs, three (1.9%) were category 3 according to Lung-RADS version 1.0, of which two (66.7%) were down-classified to category 2 with version 1.1. One of the three down-categorized GGNs (version 1.1) proved to be malignant (false-negative finding). Statistically significant improvement for Lung-RADS version 1.1 was found for total nodules (P < .01) and PFNs (P < .01), but not GGNs (P = .48). Conclusion This secondary analysis of National Lung Screening Trial data shows that Lung Imaging Reporting and Data System version 1.1 decreased the number of false-positive results. This was related to the down-classification of perifissural nodules in the range of 6 up to 10 mm. The increase in allowable nodule size for ground-glass nodules in category 2 from 20 mm (version 1.0) to 30 mm (version 1.1) showed no benefit. © RSNA, 2021 See also the editorial by Mayo and Lam in this issue.

Lung-RADS Version 1.1: Challenges and a Look Ahead, From the AJR Special Series on Radiology Reporting and Data Systems.

In 2014, the American College of Radiology (ACR) created Lung-RADS 1.0. The system was updated to Lung-RADS 1.1 in 2019, and further updates are anticipated as additional data become available. Lung-RADS provides a common lexicon and standardized nodule follow-up management paradigm for use when reporting lung cancer screening (LCS) low-dose CT (LDCT) chest examinations and serves as a quality assurance and outcome monitoring tool. The use of Lung-RADS is intended to improve LCS performance and lead to better patient outcomes. To date, the ACR's Lung Cancer Screening Registry is the only LCS registry approved by the Centers for Medicare & Medicaid Services and requires the use of Lung-RADS categories for reimbursement. Numerous challenges have emerged regarding the use of Lung-RADS in clinical practice, including the timing of return to LCS after planned follow-up diagnostic evaluation; potential substitution of interval diagnostic CT for future LDCT; role of volumetric analysis in assessing nodule size; assessment of nodule growth; assessment of cavitary, subpleural, and category 4X nodules; and variability in reporting of the S modifier. This article highlights the major updates between versions 1.0 and 1.1 of Lung-RADS, describes the system's ongoing challenges, and summarizes current evidence and recommendations.

A Case-Based Review of Vaping-Induced Injury-Pulmonary Toxicity and Beyond.

The last 10 years has seen a steady rise in the use of electronic cigarettes ("e-cigarettes" or ECIGs) or "vape pens." Though initially developed to assist with smoking cessation, use among adolescents has been particularly high. A concomitant rise in ECIG-related injuries disproportionately affecting young patients has been recognized. This unique case series highlights both pulmonary and extra-pulmonary ECIG-induced injuries including vape tip ingestion, maxillofacial fractures after vape pen explosion, myocarditis, and several different manifestations of vaping-associated lung injury. Becoming familiar with expected imaging findings in the wide array of ECIG-induced complications will help radiologists recognize these findings, recommend further imaging as needed, facilitate early diagnosis by help referring clinicians elicit the relevant history from patients, and expedite appropriate treatment.

Organizing pneumonia co-existing with carcinoid tumour: complete resolution with bronchoscopic tumour resection.

Organizing pneumonia is a well-known clinical entity resulting in response to noxious stimuli causing lung injury. It is known to occur with infectious disease processes, neoplasms, post lung surgery or radiation therapy and when idiopathic, is called cryptogenic organizing pneumonia. We present an unusual case of a 48-year-old woman who presented with chronic cough and progressive dyspnoea while being on macrolide therapy for Lyme disease. Computerized tomography of chest demonstrated a well-circumscribed nodule in the lingula and bilateral central ground glass opacities. Transbronchial biopsies were consistent with carcinoid tumour in the lingula and organizing pneumonia in bilateral lung fields. Bronchoscopic relief of obstruction was performed by mechanical debulking of the tumour, with subsequent complete resolution of bilateral opacities, consistent with resolution of organizing pneumonia without the need for steroid therapy.

Missed Lung Cancer.

The chest radiograph is one of the most commonly used imaging studies and is the modality of choice for initial evaluation of many common clinical scenarios. Over the last two decades, chest computed tomography has been increasingly used for a wide variety of indications, including respiratory illnesses, trauma, oncologic staging, and more recently lung cancer screening. Diagnostic radiologists should be familiar with the common causes of missed lung cancers on imaging studies in order to avoid detection and interpretation errors. Failure to detect these lesions can potentially have serious implications for both patients as well as the interpreting radiologist.

Modern Perforator Flap Imaging with High-Resolution Blood Pool MR Angiography.

Advances in microsurgical techniques have improved autologous reconstructions by providing new donor site options while decreasing donor site morbidity. Various preoperative imaging modalities have been studied to assess the relevant vascular anatomic structures, with magnetic resonance (MR) angiography traditionally lagging behind computed tomography (CT) with respect to spatial resolution. Blood pool MR angiography with gadofosveset trisodium, a gadolinium-based contrast agent with extended intravascular retention, has allowed longer multiplanar acquisitions with resultant voxel sizes similar to or smaller than those of CT and with improved signal-to-noise ratio and soft-tissue contrast while maintaining the ability to depict flow with time-resolved imaging. The resultant vascular detail enables precise evaluation of the relevant vascular anatomic structures, including the vessel course, size, and branching pattern, as well as the venous arborization pattern. In addition, any architectural distortion, vessel alteration, or injury from prior surgery can be depicted. The reporting radiologist should be aware of pertinent and incidental findings relevant to the planned surgery and the patient's disease so that he or she can assist the microsurgeon in flap design as a member of the multidisciplinary team. Given the lack of ionizing radiation exposure in patients who often have an elevated body mass index, high-spatial-resolution blood pool MR angiography has become the imaging reference standard for the preoperative assessment of perforator flap vascular and soft-tissue morphology in our practice.

The laminin alpha-1 chain derived peptide, AG73, increases fibronectin levels in breast and melanoma cancer cells.

Laminin-111 promotes the malignant phenotype, and a 12-mer synthetic peptide (AG73, RKRLQVQLSIRT) from the carboxyl terminus of the alpha1 chain increases B16F10 melanoma metastasis to the lung and liver. Using an antibody array, fibronectin was identified as an up-regulated protein in B16F10 cells after incubation with this peptide. The increased fibronectin is cell-associated with no increase in soluble fibronectin. The AG73 peptide increased the number and size of bone metastases with both B16F10 melanoma and MDA-231 breast carcinoma cells in an intracardiac injection model. Using siRNA transfection, we found that a reduction in fibronectin expression did not reduce bone metastasis in the presence of the metastasis-promoting peptide AG73. We conclude that the laminin peptide AG73 increases metastasis independently of fibronectin expression.

Heparanase cleavage of perlecan heparan sulfate modulates FGF10 activity during ex vivo submandibular gland branching morphogenesis.

Heparan sulfate proteoglycans are essential for biological processes regulated by fibroblast growth factors (FGFs). Heparan sulfate (HS) regulates the activity of FGFs by acting as a coreceptor at the cell surface, enhancing FGF-FGFR affinity, and being a storage reservoir for FGFs in the extracellular matrix (ECM). Here we demonstrate a critical role for heparanase during mouse submandibular gland (SMG) branching morphogenesis. Heparanase, an endoglycosidase, colocalized with perlecan in the basement membrane and in epithelial clefts of SMGs. Inhibition of heparanase activity in organ culture decreased branching morphogenesis, and this inhibition was rescued specifically by FGF10 and not by other FGFs. By contrast, exogenous heparanase increased SMG branching and MAPK signaling and, surprisingly, when isolated epithelia were cultured in a three-dimensional ECM with FGF10, it increased the number of lateral branches and end buds. In a solid-phase binding assay, an FGF10-FGFR2b complex was released from the ECM by heparanase. In addition, surface plasmon resonance (SPR) analysis showed that FGF10 and the FGF10-FGFR2b complex bound to purified perlecan HS and could be released by heparanase. We used the FGF10-FGFR2b complex as a probe for HS in SMGs, and it colocalized with perlecan in the basement membrane and partly colocalized with syndecan 1 in the epithelium, and binding was reduced by treatment with heparanase. In summary, our results show heparanase releases FGF10 from perlecan HS in the basement membrane, increasing MAPK signaling, epithelial clefting, and lateral branch formation, which results in increased branching morphogenesis.

Laminin alpha5 chain metastasis- and angiogenesis-inhibiting peptide blocks fibroblast growth factor 2 activity by binding to the heparan sulfate chains of CD44.

Recently, we reported that the laminin alpha5 synthetic peptide A5G27 (RLVSYNGIIFFLK, residues 2,892-2,904) binds to the CD44 receptor of B16-F10 melanoma cells via the glycosaminoglycans on CD44 and inhibits tumor cell migration, invasion, and angiogenesis in a dominant-negative manner. Here, we have identified the potential mechanism of A5G27 activity using WiDr human colorectal carcinoma cells. WiDr cells bound to the laminin A5G27 peptide via the heparin-like and chondroitin sulfate B glycosaminoglycan side chains of CD44. Cell binding to fibroblast growth factor (FGF2) was blocked by laminin peptide A5G27 but not by either a scrambled version of this peptide or by another laminin peptide known to bind cell surface proteoglycans. FGF2 signaling involving tyrosine phosphorylation was also blocked by laminin peptide A5G27 but was not affected by peptide controls. Finally, we have shown that peptide A5G27 directly blocks FGF2 binding to heparin. Peptide A5G27 has sequence homology to a region on FGF2 that binds heparin and the FGF receptor and is important in FGF2 central cavity formation. We conclude that peptide A5G27 inhibits metastasis and angiogenesis by blocking FGF2 binding to the heparan sulfate side chains of CD44 variant 3, thus decreasing FGF2 bioactivity.