Lung Cancer Screening Using Clinical Photon-Counting Detector Computed Tomography and Energy-Integrating-Detector Computed Tomography: A Prospective Patient Study.

OBJECTIVE: To evaluate the diagnostic quality of photon-counting detector (PCD) computed tomography (CT) in patients undergoing lung cancer screening compared with conventional energy-integrating detector (EID) CT in a prospective multireader study. MATERIALS: Patients undergoing lung cancer screening with conventional EID-CT were prospectively enrolled and scanned on a PCD-CT system using similar automatic exposure control settings and reconstruction kernels. Three thoracic radiologists blinded to CT system compared PCD-CT and EID-CT images and scored examinations using a 5-point Likert comparison score (-2 [left image is worse] to +2 [left image is better]) for artifacts, sharpness, image noise, diagnostic image quality, emphysema visualization, and lung nodule evaluation focusing on the border. Post hoc correction of Likert scores was performed such that they reflected PCD-CT performance in comparison to EID-CT. A nonreader radiologist measured objective image noise. RESULTS: Thirty-three patients (mean, 66.9 ± 5.6 years; 11 female; body mass index; 30.1 ± 5.1 kg/m 2 ) were enrolled. Mean volume CT dose index for PCD-CT was lower (0.61 ± 0.21 vs 0.73 ± 0.22; P < 0.001). Pooled reader results showed significant differences between imaging modalities for all comparative rankings ( P < 0.001), with PCD-CT favored for sharpness, image noise, image quality, and emphysema visualization and lung nodule border, but not artifacts. Photon-counting detector CT had significantly lower image noise (74.4 ± 10.5 HU vs 80.1 ± 8.6 HU; P = 0.048). CONCLUSIONS: Photon-counting detector CT with similar acquisition and reconstruction settings demonstrated improved image quality and less noise despite lower radiation dose, with improved ability to depict pulmonary emphysema and lung nodule borders compared with EID-CT at low-dose lung cancer CT screening.

Clinical Outcomes With and Without Plasma Exchange in the Treatment of Rapidly Progressive Interstitial Lung Disease Associated With Idiopathic Inflammatory Myopathy.

BACKGROUND/OBJECTIVE: A subset of patients with idiopathic inflammatory myopathy (IIM) develops highly fatal, rapidly progressive interstitial lung disease (RP-ILD). Treatment strategies consist of glucocorticoid and adjunctive immunosuppressive therapies. Plasma exchange (PE) is an alternative therapy, but its benefit is unclear. In this study, we aimed to determine whether PE benefited outcomes for patients with RP-ILD. METHODS: In this medical records review study, we compared baseline characteristics and clinical outcomes for 2 groups of patients with IIM-related RP-ILD: those who received and did not receive PE. RESULTS: Our cohort consisted of 15 patients, 9 of whom received PE. Baseline demographic characteristics and severity of lung, skin, and musculoskeletal disease between the 2 groups of patients were not significantly different. Five patients required mechanical ventilation (2, PE; 3, no PE). Plasma exchange was generally a third-line adjunctive treatment option. The PE group had a longer median (interquartile range) hospitalization (27.0 [23.0-36.0] days) than the non-PE group (12.0 [8.0-14.0] days) ( p = 0.02). There was a potential benefit in 30-day mortality improvement in those receiving PE (0% vs 33%, p = 0.14), with a statistically significant improvement in 2 important composite end points including 30-day mortality or need for lung transplant (0% vs 50%, p = 0.04) and 1-year mortality or need for lung transplant or hospital readmission for RP-ILD in those receiving PE (22% vs 83%, p = 0.04). CONCLUSIONS: Plasma exchange may be an underutilized, safe salvage therapy for patients with IIM-related RP-ILD when other immunosuppressive therapies fail.

Idiopathic pulmonary fibrosis: CT and risk of death.

PURPOSE: To investigate the prognostic value of quantitative computed tomographic (CT) scoring for the extent of fibrosis or emphysema in the context of a clinical model that includes the gender, age, and physiology ( GAP gender, age, and physiology model) of the patient. MATERIALS AND METHODS: Study cohorts were approved by local institutional review boards, and all patients provided written consent. This was a retrospective cohort study that included 348 patients (246 men, 102 women; mean age, 69 years ± 9) with idiopathic pulmonary fibrosis from two institutions. Fibrosis and emphysema visual scores were independently determined by two radiologists. Models were based on competing risks regression for death and were evaluated by using the C index and reclassification improvement. RESULTS: The CT- GAP gender, age, and physiology model (a modification of the original GAP gender, age, and physiology model that replaces diffusion capacity of carbon monoxide with CT fibrosis score) had accuracy comparable to that of the original GAP gender, age, and physiology model, with a C index of 70.3 (95% confidence interval: 66.4, 74.0); difference in C index compared with the GAP gender, age, and physiology model of -0.4 (95% confidence interval: -2.2, 3.4). The performance of the original GAP gender, age, and physiology model did not change significantly with the simple addition of fibrosis score, with a change in C index of 0.0 (95% confidence interval: -1.8, 0.5) or of emphysema score, with a change in C index of 0.0 [95% confidence interval: -1.3, 0.4]). CONCLUSION: CT fibrosis score can replace diffusion capacity of carbon monoxide test results in a modified GAP gender, age, and physiology model (the CT- GAP gender, age, and physiology model) with comparable performance. This may be a useful alternative model in situations where CT scoring is more reliable and available than diffusion capacity of carbon monoxide.

Automated quantification of radiological patterns predicts survival in idiopathic pulmonary fibrosis.

Accurate assessment of prognosis in idiopathic pulmonary fibrosis remains elusive due to significant individual radiological and physiological variability. We hypothesised that short-term radiological changes may be predictive of survival. We explored the use of CALIPER (Computer-Aided Lung Informatics for Pathology Evaluation and Rating), a novel software tool developed by the Biomedical Imaging Resource Laboratory at the Mayo Clinic Rochester (Rochester, MN, USA) for the analysis and quantification of parenchymal lung abnormalities on high-resolution computed tomography. We assessed baseline and follow-up (time-points 1 and 2, respectively) high-resolution computed tomography scans in 55 selected idiopathic pulmonary fibrosis patients and correlated CALIPER-quantified measurements with expert radiologists' assessments and clinical outcomes. Findings of interval change (mean 289 days) in volume of reticular densities (hazard ratio 1.91, p=0.006), total volume of interstitial abnormalities (hazard ratio 1.70, p=0.003) and per cent total interstitial abnormalities (hazard ratio 1.52, p=0.017) as quantified by CALIPER were predictive of survival after a median follow-up of 2.4 years. Radiologist interpretation of short-term global interstitial lung disease progression, but not specific radiological features, was also predictive of mortality. These data demonstrate the feasibility of quantifying interval short-term changes on high-resolution computed tomography and their possible use as independent predictors of survival in idiopathic pulmonary fibrosis.

Leukemic pulmonary infiltrates in chronic lymphocytic leukemia: Clinical and imaging features.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in Western countries. Although various patterns of lung involvement with CLL have been reported, data on clinicoradiologic presentation are sparse. METHODS: A computer-assisted search was conducted to identify patients encountered at Mayo Clinic from 1998 to 2022 and had leukemic pulmonary infiltrates (LPI) with CLL demonstrated on lung biopsy. Medical records and chest imaging studies were reviewed to identify clinical and radiologic features. RESULTS: Among 13 patients, median age was 77 years (range: 60-88) and included 10 men (77 %). All patients were known to have CLL with a median duration of 96 months (range: 50-408), and none were on treatment. Most common symptoms were dyspnea (62 %), cough (54 %), and fatigue (46 %); 2 patients (15 %) were asymptomatic. Dominant abnormality on CT consisted of single or multiple nodular/mass-like opacities in 10 patients (77 %), while diffuse centrilobular nodules, pleural mass, and diffuse bronchial wall thickening were each seen in one patient, respectively; intrathoracic lymphadenopathy was present in all. After diagnosis of LPI, treatment for CLL was administered to 7 patients (54 %); 6 patients (86 %) exhibited improvement. During follow-up (median 41 months), 8 (62 %) patients died. Causes of death included progressive CLL or treatment-related complications (2 patients), pneumonia (1 patient), unrelated causes (3 patients), and unknown in 2 patients. CONCLUSIONS: LPI in CLL is generally encountered in patients with known untreated CLL. The main imaging feature is single mass-like opacity or multiple nodular/mass-like opacities, associated with intrathoracic lymphadenopathy.

Clinical, radiologic, and pathologic features and outcomes of pulmonary transthyretin amyloidosis.

INTRODUCTION: Amyloid transthyretin amyloidosis (ATTR) is characterized by deposition of a misfolded conformation of the transport protein TTR, most commonly in cardiac and nerve tissue, causing clinical disease. Pulmonary amyloidosis, or deposition of ATTR in lung tissue, is a poorly characterized manifestation of this disease. We present the clinical course, imaging characteristics, pathology results, and outcomes of a patient cohort diagnosed with pulmonary ATTR. METHODS: We retrospectively reviewed records of 28 patients with pulmonary ATTR seen at Mayo Clinic from September 30, 2005, through December 31, 2020. Data collected included information on demographics, subjective symptoms, tissue biopsy results, pulmonary function testing, imaging findings, and treatment. RESULTS: Of the patients, 89% were men; the median age was 74.5 years (range, 50-99 years). Patients were typically diagnosed after persistent dyspnea and abnormal chest imaging resulted in lung biopsy, which yielded the ATTR diagnosis. Most patients had a preexisting diagnosis of cardiac ATTR. The disease was wild-type in 62% and hereditary in 38%. Normal pulmonary function tests followed by a restrictive pattern were the most common presentation. Of the patients, 93% had chest computed tomography, with common findings of diffuse nodularity, calcified granulomas, interlobular septal thickening, and pleural effusions. Almost all patients had pulmonary vascular involvement, and half had interstitial involvement on tissue biopsy. One-third received either anti-amyloid pharmacotherapy or a heart transplant. Half of patients had died before the time of study inclusion. CONCLUSION: Pulmonary disease is a less common but clinically important manifestation of ATTR.

Estimating the Clinical Impact of Photon-Counting-Detector CT in Diagnosing Usual Interstitial Pneumonia.

OBJECTIVE: The aim of this study was to evaluate the clinical impact of a higher spatial resolution, full field-of-view investigational photon-counting detector computed tomography (PCD-CT) on radiologist confidence in imaging findings and diagnosis of usual interstitial pneumonia (UIP) compared with conventional energy-integrating detector CT (EID-CT). MATERIALS AND METHODS: Patients suspected of interstitial lung disease were scanned on a PCD-CT system after informed consent and a clinically indicated EID-CT. In 2 sessions, 3 thoracic radiologists blinded to clinical history and scanner type evaluated CT images of the right and left lungs separately on EID- or PCD-CT, reviewing each lung once/session, rating confidence in imaging findings of reticulation, traction bronchiectasis, honeycombing, ground-glass opacities (GGOs), mosaic pattern, and lower lobe predominance (100-point scale: 0-33, likely absent; 34-66, indeterminate; 67-100, likely present). Radiologists also rated confidence for the probability of UIP (0-20, normal; 21-40, inconsistent with UIP; 41-60, indeterminate UIP; 61-81; probable UIP; 81-100, definite UIP) and graded image quality. Because a confidence scale of 50 represented completely equivocal findings, magnitude score (the absolute value of confidence scores from 50) was used for analysis (higher scores were more confident). Image noise was measured for each modality. The magnitude score was compared using linear mixed effects regression. The consistency of findings and diagnosis between 2 scanners were evaluated using McNemar test and weighted κ statistics, respectively. RESULTS: A total of 30 patients (mean age, 68.8 ± 11.0 years; M:F = 18:12) underwent conventional EID-CT (median CTDI vol , 7.88 mGy) and research PCD-CT (median CTDI vol , 6.49 mGy). The magnitude scores in PCD-CT were significantly higher than EID-CT for imaging findings of reticulation (40.7 vs 38.3; P = 0.023), GGO (34.4 vs 31.7; P = 0.019), and mosaic pattern (38.6 vs 35.9; P = 0.013), but not for other imaging findings ( P ≥ 0.130) or confidence in UIP (34.1 vs 22.2; P < 0.059). Magnitude score of probability of UIP in PCD-CT was significantly higher than EID-CT in one reader (26.0 vs 21.5; P = 0.009). Photon-counting detector CT demonstrated a decreased number of indeterminate GGO (17 vs 26), an increased number of unlikely GGO (74 vs 50), and an increased number of likely reticulations (140 vs 130) relative to EID-CT. Interobserver agreements among 3 readers for imaging findings and probability of UIP were similar between PCD-CT and EID-CT (intraclass coefficient: 0.507-0.818 vs 0.601-0.848). Photon-counting detector CT had higher scores in overall image quality (4.84 ± 0.38) than those in EID-CT (4.02 ± 0.40; P < 0.001) despite increased image noise (mean 85.5 vs 36.1 HU). CONCLUSIONS: Photon-counting detector CT provided better image quality and improved the reader confidence for presence or absence of imaging findings of reticulation, GGO, and mosaic pattern with idiosyncratic improvement in confidence in UIP presence.

Inappropriate application of nodule management guidelines in radiologist reports before and after revision of exclusion criteria.

OBJECTIVE: The purpose of this study was to retrospectively evaluate appropriate and inappropriate application of nodule management guidelines in radiology reports of pulmonary nodules seen at CT. MATERIALS AND METHODS: The CT reports of 181 patients examined in July and August 2007 (94 males, 87 females; age range, 2-88 years; mean, 60.3 ± 13.0 years) and 177 patients examined in March 2009 (106 men, 71 women; age range, 24-91 years; mean, 60.7 ± 14.0 years) were retrospectively reviewed to assess whether nodule management guidelines were inappropriately applied. The exclusion criteria for the 2007 cases included multiple nodules, stable nodules, potential metastatic disease, probable infectious or inflammatory cause, and age younger than 35 years. The exclusion criteria for the 2009 cases were all of the 2007 criteria except multiple nodules. RESULTS: Guidelines were inappropriately applied 105 times in 2007 and 25 times in 2009. Reasons for inappropriate use in 2007 were multiple nodules in 70 of the 105 cases (67%), potential metastatic disease in 25 cases (24%), age younger than 35 years in four cases (4%), stable nodules in two cases (2%), probable infectious or inflammatory cause in two cases (2%), and protocol not included despite absence of exclusion criteria in two cases (2%). The reasons in 2009 were potential metastatic disease in 15 of the 25 cases (60%), age younger than 35 years in four cases (16%), stable nodules in three cases (12%), probable infectious or inflammatory cause in one case (4%), and protocol not included despite absence of exclusion criteria in two cases (8%). The percentage of cases with at least one error was 48.1% in 2007, significantly higher than the 13.6% in 2009 (p < 0.001). CONCLUSION: Inappropriate application of guidelines for management of pulmonary nodules seen at CT was significantly reduced by removing multiple nodules from the exclusion criteria. Otherwise, causes for inappropriate application remained stable.

Presenting Clinicoradiologic Features, Causes, and Clinical Course of Exogenous Lipoid Pneumonia in Adults.

BACKGROUND: Exogenous lipoid pneumonia (ELP) develops when lipid-containing substances enter the airways through aspiration or inhalation and incite an inflammatory response. The diagnosis of ELP often is difficult because findings may be nonspecific. The clinical course of ELP has not been well characterized. RESEARCH QUESTION: What are the presenting clinicoradiologic features of ELP, its causative agents, and clinical course? STUDY DESIGN AND METHODS: We searched the Mayo Clinic electronic medical records for patients diagnosed with ELP between 1998 and 2020. Inclusion diagnostic criteria were: (1) lipoid pneumonia (LP) on histopathologic examination, (2) lipid-laden macrophages in BAL fluid, or (3) fatty attenuation of parenchymal opacities on chest CT imaging. Additionally, all patients were required to have a clinician diagnosis of LP in the absence of conditions known to cause endogenous LP. RESULTS: Thirty-four patients were identified. Mean age was 71 years, with no sex predominance; one-half were asymptomatic. The diagnosis was confirmed by lung biopsy (including three lobectomies for suspected malignancy) in 71% of patients, CT scan in 24% of patients, and BAL in 5% of patients. Most patients manifested bilateral parenchymal opacities that commonly involved the lower lobes; fatty attenuation was identifiable in only 41% of patients. A causative substance was identified in 79% of patients, in most cases after the diagnosis was established. Over a median follow-up of 1.2 years, only 20% of patients with chronic respiratory symptoms improved, whereas 50% worsened. Over a median follow-up interval of 1 year, CT scan abnormalities improved or resolved in 33% of patients and progressed in 39% of patients. Patients who deteriorated were older, with a higher prevalence of GI disorders than those who remained stable or improved. INTERPRETATION: ELP often is asymptomatic and may not manifest fatty attenuation on chest CT imaging. Clinical and radiologic abnormalities persist or worsen in most affected patients, even when the causative agent is discontinued.

Pathology, Radiology, and Genetics of Interstitial Lung Disease in Patients With Shortened Telomeres.

Interstitial lung diseases (ILDs) in patients with shortened telomeres have not been well characterized. We describe demographic, radiologic, histopathologic, and molecular features, and p16 expression in patients with telomeres ≤10th percentile (shortened telomeres) and compare them to patients with telomere length >10th percentile. Lung explants, wedge biopsies, and autopsy specimens of patients with telomere testing were reviewed independently by 3 pathologists using defined parameters. High-resolution computed tomography scans were reviewed by 3 radiologists. p16-positive fibroblast foci were quantified. A multidisciplinary diagnosis was recorded. Patients with shortened telomeres (N=26) were morphologically diagnosed as usual interstitial pneumonia (UIP) (N=11, 42.3%), chronic hypersensitivity pneumonitis (N=6, 23.1%), pleuroparenchymal fibroelastosis, fibrotic nonspecific interstitial pneumonia, desquamative interstitial pneumonia (N=1, 3.8%, each), and fibrotic interstitial lung disease (fILD), not otherwise specified (N=6, 23.1%). Patients with telomeres >10th percentile (N=18) showed morphologic features of UIP (N=9, 50%), chronic hypersensitivity pneumonitis (N=3, 16.7%), fibrotic nonspecific interstitial pneumonia (N=2, 11.1%), or fILD, not otherwise specified (N=4, 22.2%). Patients with shortened telomeres had more p16-positive foci (P=0.04). The number of p16-positive foci correlated with outcome (P=0.0067). Thirty-nine percent of patients with shortened telomeres harbored telomere-related gene variants. Among 17 patients with shortened telomeres and high-resolution computed tomography features consistent with or probable UIP, 8 (47.1%) patients showed morphologic features compatible with UIP; multidisciplinary diagnosis most commonly was idiopathic pulmonary fibrosis (N=7, 41.2%) and familial pulmonary fibrosis (N=5, 29%) in these patients. In conclusion, patients with shortened telomeres have a spectrum of fILDs. They often demonstrate atypical and discordant features on pathology and radiology leading to diagnostic challenges.

Managing Incidental Findings on Thoracic CT: Lung Findings. A White Paper of the ACR Incidental Findings Committee.

The ACR Incidental Findings Committee presents recommendations for managing incidentally detected lung findings on thoracic CT. The Chest Subcommittee is composed of thoracic radiologists who endorsed and developed the provided guidance. These recommendations represent a combination of current published evidence and expert opinion and were finalized by informal iterative consensus. The recommendations address commonly encountered incidental findings in the lungs and are not intended to be a comprehensive review of all pulmonary incidental findings. The goal is to improve the quality of care by providing guidance on management of incidentally detected thoracic findings.

Iron deposition and increased alveolar septal capillary density in nonfibrotic lung tissue are associated with pulmonary hypertension in idiopathic pulmonary fibrosis.

BACKGROUND: Early diagnosis of pulmonary hypertension (PH) in idiopathic pulmonary fibrosis (IPF) has potential prognostic and therapeutic implications but can be difficult due to the lack of specific clinical manifestations or accurate non-invasive tests. Histopathologic parameters correlating with PH in IPF are also not known. Remodeling of postcapillary pulmonary vessels has been reported in the nonfibrotic areas of explanted lungs from IPF patients. We hypothesized that iron deposition and increased alveolar capillaries, the findings often seen in postcapillary PH, might predict the presence of clinical PH, independent of the severity of fibrosis or ventilatory dysfunction in IPF patients. To test this hypothesis, we examined the association between these histologic parameters and the degree of PH, with consideration of the severity of disease in IPF. METHODS: Iron deposition and alveolar septal capillary density (ASCD) were evaluated on histologic sections with hematoxylin-eosin, iron, elastin and CD34 stainings. Percentage of predicted forced vital capacity (FVC%) was used for grading pulmonary function status. Fibrosis score assessed on high resolution computed tomography (HRCT) was used for evaluating overall degree of fibrosis in whole lungs. Right ventricular systolic pressure (RVSP) by transthoracic echocardiography was used for the estimation of PH. Univariate and multivariate regression analyses were performed. RESULTS: A cohort of 154 patients was studied who had the clinicopathological diagnosis of IPF with surgical lung biopsies or explants during the period of 1997 to 2006 at Mayo Clinic Rochester. In univariate analysis, RVSP in our IPF cases was associated with both iron deposition and ASCD (p < 0.001). In multivariate analysis with FVC% and HRCT fibrosis score included, iron deposition (p = 0.02), but not ASCD (p = 0.076), maintained statistically significant association with RVSP. FVC% was associated with RVSP on univariate analysis but not on multivariate analysis, while fibrosis score lacked any association with RVSP by either univariate or multivariate analyses. CONCLUSIONS: Iron deposition and ASCD in non fibrotic lung tissue showed an association with RVSP, suggesting that these features are possible morphologic predictors of PH in IPF.

Pulmonary nodules in patients with primary Sjögren's syndrome: Causes, clinico-radiologic features, and outcomes.

BACKGROUND: Primary Sjögren's Syndrome (pSS) is characterized by an immune-mediated lymphoplasmacytic infiltration of the salivary and lacrimal glands. Pulmonary nodules are not uncommonly encountered in these patients. METHODS: We conducted a retrospective computer-assisted search for patients with pSS who were encountered at our institution between 1999 and 2018 and had histologically characterized pulmonary nodule(s)/mass (es) (PNs). RESULTS: Of 41 patients with pSS and PNs, median age was 67 years (IQR, 56-74), 94% were women, and 39% had a smoking history. The PNs proved to be non-Hodgkin lymphoma (NHL) in 16 patients (39%), lung carcinoma in 11 patients (27%), other malignancies in 2 patients (5%), and benign diseases in remaining 12 patients (29%), including 7 with amyloidomas. Patients with NHL were younger (p = 0.006) while smoking exposure was more prevalent in patients with lung carcinoma (p = 0.022). Patients with NHL had a higher number of PNs and more often manifested random distribution, cysts, ground-glass changes and consolidations. Upper and/or mid-lung location, spiculated borders, solitary nodule, increasing size, and higher SUVmean on FDG-PET scan were associated with lung carcinoma. At the end of follow-up (median 5.9 years), 8 patients (20%) had died and included 5 patients with lung carcinoma; no deaths were observed in the NHL group. CONCLUSIONS: The majority of biopsied PNs in patients with pSS were malignant, most commonly lymphomas. Smoking exposure, solitary nodule, and high FDG avidity were more frequently associated with lung carcinoma. The clinical context, CT and 18FDG-PET are complementary in the evaluation and management of PNs in patients with pSS.

Idiopathic nonspecific interstitial pneumonia: report of an American Thoracic Society project.

RATIONALE: The 2002 American Thoracic Society/European Respiratory Society classification of idiopathic interstitial pneumonias identified nonspecific interstitial pneumonia (NSIP) as a provisional diagnosis. Concern was expressed that NSIP was a "wastebasket" category, difficult to distinguish from other idiopathic interstitial pneumonias. OBJECTIVES: The following questions were addressed: (1) Is idiopathic NSIP a distinct entity? 2) If so, what are its clinical, radiologic and pathologic characteristics? (3) What is the role of radiology and pathology in establishing the diagnosis? (4) To make a diagnosis of idiopathic NSIP, what other disorders need to be excluded and how should this be done? METHODS: Investigators who had previously reported cases of idiopathic NSIP were invited to submit cases for review (n = 305). After initial review, cases with complete clinical, radiologic, and pathologic information (n = 193) were reviewed in a series of workshops. MEASUREMENTS AND MAIN RESULTS: Sixty-seven cases were identified as NSIP. Mean age was 52 years, 67% were women, 69% were never-smokers, and 46% were from Asian countries. The most common symptoms were dyspnea (96%) and cough (87%); 69% had restriction. By high-resolution computed tomography, the lower lung zones were predominantly involved in 92% of cases; 46% had a peripheral distribution; 47% were diffuse. Most showed a reticular pattern (87%) with traction bronchiectasis (82%) and volume loss (77%). Lung biopsies showed uniform thickening of alveolar walls with a spectrum of cellular to fibrosing patterns. Five-year survival was 82.3%. CONCLUSIONS: Idiopathic NSIP is a distinct clinical entity that occurs mostly in middle-aged women who are never-smokers. The prognosis of NSIP is very good.

Clinico-radiologic Features of Lung Disease Associated With Aspiration Identified on Lung Biopsy.

BACKGROUND: Aspiration-related lung diseases are commonly diagnosed presumptively based on the clinical context and radiologic findings. Limited data exist on the spectrum of clinico-radiologic presentations associated with aspiration. METHODS: This study reviewed all cases of aspiration identified on lung biopsy encountered at the Mayo Clinic between 2003 and 2017. Demographic and clinical features, including risk factors for aspiration, diagnoses suspected prior to biopsy, imaging findings, and microbiologic data, were analyzed. RESULTS: A total of 52 consecutive adult cases of aspiration identified on lung biopsy (histologic presence of food or other particulate matter) were included; patients' median age was 59 years (range, 22 to 79 years), 38% were women, and there were five lung transplant recipients. Of these, 63% were diagnosed according to results of surgical biopsy (including four cases of lobectomy) and 37% according to results of transbronchial biopsy. Aspiration was clinically suspected prior to biopsy in 35% of the subjects. Ninety percent of subjects had at least one identifiable risk factor for aspiration; gastroesophageal reflux disease was the most common (62%), followed by a structurally abnormal esophagogastric tract and the use of consciousness-impairing medications. Only 27% of patients reported dysphagia or choking. Chest CT imaging revealed a variety of parenchymal patterns, including bronchiolitis (42%), patchy consolidation (19%), and mass (15%). Of 25 patients undergoing a video-swallow evaluation, 14 (56%) had abnormal results with laryngeal penetration with or without aspiration. Microbial cultures obtained in 21 lung biopsy specimens yielded no pathogens. CONCLUSIONS: Aspiration can occur in the absence of subjective or demonstrable swallowing difficulties and manifest a broad spectrum of clinico-radiologic presentations.

Clinical and Histopathologic Features of Immune Checkpoint Inhibitor-related Pneumonitis.

Immune checkpoint inhibitors (ICIs) have revolutionized oncology, but are associated with immune-related adverse events. Clinically, pneumonitis is a well-recognized complication, but its histopathologic features are poorly understood. Institutional archives were searched for patients having ICI therapy and subsequent lung tissue sampling. After excluding infectious cases, 9 patients (5 women, median: 59 y) were identified with clinically suspected ICI-related pneumonitis. Clinical history, imaging, and pathology slides were reviewed. Patients received pembrolizumab (6 cases), nivolumab (1), ipilimumab followed by pembrolizumab (1), or pembrolizumab followed by nivolumab (1); the latter experienced pneumonitis with both agents. Treatment duration ranged from 1 to 33 cycles (median: 8). Three patients received concurrent chemotherapy and 1 received radiation; the remainder received ICI monotherapy. Symptoms were nonspecific; 2 patients were asymptomatic. Thoracic imaging showed bilateral ground glass or nodular opacities in all cases, often with pleural effusion. Histologically, organizing pneumonia was seen in 7 patients, all with subclinical or mild disease, admixed with vague non-necrotizing airspace granulomas in 3 cases; all 6 patients with follow-up did well. One patient had acute fibrinous pneumonitis and 1 had diffuse alveolar damage; both died. All 9 cases showed foamy macrophages and pneumocyte vacuolization; 6 had rare eosinophils. ICI-related pneumonitis presents as bilateral ground-glass opacities or nodules, and usually manifests as organizing pneumonia histopathologically, often with vague non-necrotizing airspace granulomas. Foamy macrophages and pneumocyte vacuolization are characteristic and rare eosinophils are often seen. Less commonly, acute fibrinous pneumonitis or diffuse alveolar damage can occur, which may be fatal.

High-resolution CT findings of parenchymal fibrosis correlate with prognosis in hypersensitivity pneumonitis.

BACKGROUND: Histopathologic evidence of fibrosis on surgical lung biopsy has been associated with reduced survival in patients with hypersensitivity pneumonitis (HP). Changes of pulmonary fibrosis detected on CT may also correlate with prognosis in patients with HP. METHODS: We identified 69 consecutive patients with HP diagnosed between January 1997 and December 2002 at Mayo Clinic, Rochester, MN. Patients were stratified into fibrotic and nonfibrotic groups based on the CT findings. Fibrosis was defined by the presence of irregular linear opacities, traction bronchiectasis, or honeycombing. MEASUREMENTS AND MAIN RESULTS: Of 69 patients, 26 were classified as fibrotic and 43 as nonfibrotic. Patients in the fibrotic group were older, had longer symptom duration, were more likely to have crackles on auscultation, more likely to be exposed to avian antigen, and had greater restrictive lung impairment (p<0.05 for all comparisons). There were 11 deaths in the fibrotic group and 1 death in the nonfibrotic group (p<0.0001). In the regression analysis, CT evidence of fibrosis, more severe pulmonary function abnormalities, and the presence of crackles on auscultation were predictive of reduced survival (p<0.05 for all). The presence as well as the extent of fibrosis on CT was associated with increased mortality. The age-adjusted hazard ratio for mortality in patients with fibrosis was 4.6 (95% confidence interval, 2.0 to 20.1; p<0.0001). CONCLUSION: CT findings of parenchymal fibrosis are associated with reduced survival in patients with HP and may serve as a useful prognostic indicator.

Profusion of fibroblast foci in patients with idiopathic pulmonary fibrosis does not predict outcome.

RATIONALE: The prognostic significance of fibroblast foci in surgical lung biopsies from patients with idiopathic pulmonary fibrosis (IPF) is unclear. OBJECTIVES: We assessed the relationship between profusion of fibroblast foci and survival in 43 patients with IPF seen at a tertiary referral medical center from 1996 to 2002. METHODS: Fibroblast foci in surgical lung biopsies were counted using a systematic morphometric point-counting technique. Patients with either clinical or pathologic evidence of accelerated disease were excluded from analysis. The association of fibroblast counts with survival was assessed using proportional hazards regression. RESULTS: The mean age (+/-SD) of the study population was 64+/-9 years; 26 (60%) patients were male. The mean (%+/-SD) profusion of fibroblastic foci was 0.6+/-0.7, expressed as a percentage of total points counted. Fibroblast foci counts did not differ markedly between upper, middle, and lower lobes. Median survival from the time of biopsy was 2.4 years; there were 25 (58%) deaths in the follow up period. There was no significant relationship between profusion of fibroblast foci and survival in the overall group (p=0.250). CONCLUSIONS: Higher prevalence of fibroblast foci assessed using a simple point-counting technique applied to surgical lung biopsies is not associated with survival in patients with clinically stable IPF.

Cowden Syndrome: A Cause of Pulmonary Cysts.

OBJECTIVE: To describe the pulmonary imaging findings in patients with Cowden syndrome (CS). MATERIALS AND METHODS: A retrospective review identified all patients with CS who underwent dedicated computed tomography examinations of the chest at our institution between January 2000 and October 2017. Patient demographics and imaging characteristics were identified through a review of the electronic medical record and relevant imaging. RESULTS: Fifteen patients (6 males/9 females; mean age 53 y) with a clinical diagnosis of CS were identified. Genetic confirmation of the PTEN mutation was available in 8/15 (50%) patients. Pulmonary cysts were present in 12/15 (80%) patients and in 8/8 (100%) patients with documented PTEN mutations. The cysts ranged in size from 4 to 63 mm and were <10 in 10/12 (83%). Cysts were distributed randomly in 10/12 (83%) cases. Solid pulmonary nodules were present in 13/15 (87%) patients and were distributed randomly in all cases. CONCLUSIONS: Pulmonary cysts and solid nodules are common in patients with CS. Cysts tend to be distributed randomly, few in number, and may have traversing vessels. These findings should not be interpreted as evidence of another underlying disorder in the setting of CS.