Human Oncoviruses and Thoracic Tumors: Understanding the Imaging Findings.

Approximately 1.4 million virus-induced cancers occur annually, representing roughly 10% of the cancer burden worldwide. Seven oncogenic DNA and RNA viruses (ie, oncoviruses) are implicated in approximately 12%-25% of all human cancers owing to a variety of mechanisms as uncommon consequences of the normal viral life cycle. These seven well-recognized human oncoviruses are Epstein-Barr virus (EBV), human T-lymphotropic virus 1, hepatitis B virus, hepatitis C virus, HIV, human papilloma virus (HPV), and human herpesvirus 8 (HHV-8). Several viruses-namely, EBV, HPV, and Kaposi sarcoma herpesvirus or HHV-8-are increasingly being recognized as being related to HIV and/or AIDS, the growing number of transplant cases, and the use of immunosuppressive therapies. Infectious and inflammatory processes, and the accompanying lymphadenopathy, are great mimickers of human oncovirus-related tumors. Although it is often difficult to differentiate these entities, the associated clinical setting and radiologic findings may provide clues for an accurate diagnosis and appropriate management. Malignant lymphoid lesions are best evaluated with multidetector chest CT. The radiologic findings of these lesions are often nonspecific and are best interpreted in correlation with clinical data and histopathologic findings. ©RSNA, 2022.

Combined Pulmonary Fibrosis and Emphysema: Pulmonary Function Testing and a Pathophysiology Perspective.

Combined pulmonary fibrosis and emphysema (CPFE) has been increasingly recognized over the past 10-15 years as a clinical entity characterized by rather severe imaging and gas exchange abnormalities, but often only mild impairment in spirometric and lung volume indices. In this review, we explore the gas exchange and mechanical pathophysiologic abnormalities of pulmonary emphysema, pulmonary fibrosis, and combined emphysema and fibrosis with the goal of understanding how individual pathophysiologic observations in emphysema and fibrosis alone may impact clinical observations on pulmonary function testing (PFT) patterns in patients with CPFE. Lung elastance and lung compliance in patients with CPFE are likely intermediate between those of patients with emphysema and fibrosis alone, suggesting a counter-balancing effect of each individual process. The outcome of combined emphysema and fibrosis results in higher lung volumes overall on PFTs compared to patients with pulmonary fibrosis alone, and the forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) ratio in CPFE patients is generally preserved despite the presence of emphysema on chest computed tomography (CT) imaging. Conversely, there appears to be an additive deleterious effect on gas exchange properties of the lungs, reflecting a loss of normally functioning alveolar capillary units and effective surface area available for gas exchange, and manifested by a uniformly observed severe reduction in the diffusing capacity for carbon monoxide (DLCO). Despite normal or only mildly impaired spirometric and lung volume indices, patients with CPFE are often severely functionally impaired with an overall rather poor prognosis. As chest CT imaging continues to be a frequent imaging modality in patients with cardiopulmonary disease, we expect that patients with a combination of pulmonary emphysema and pulmonary fibrosis will continue to be observed. Understanding the pathophysiology of this combined process and the abnormalities that manifest on PFT testing will likely be helpful to clinicians involved with the care of patients with CPFE.

Transcriptomic evidence of immune activation in macroscopically normal-appearing and scarred lung tissues in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease manifested by overtly scarred peripheral and basilar regions and more normal-appearing central lung areas. Lung tissues from macroscopically normal-appearing (IPFn) and scarred (IPFs) areas of explanted IPF lungs were analyzed by RNASeq and compared with healthy control (HC) lung tissues. There were profound transcriptomic changes in IPFn compared with HC tissues, which included elevated expression of numerous immune-, inflammation-, and extracellular matrix-related mRNAs, and these changes were similar to those observed with IPFs compared to HC. Comparing IPFn directly to IPFs, elevated expression of epithelial mucociliary mRNAs was observed in the IPFs tissues. Thus, despite the known geographic tissue heterogeneity in IPF, the entire lung is actively involved in the disease process, and demonstrates pronounced elevated expression of numerous immune-related genes. Differences between normal-appearing and scarred tissues may thus be driven by deranged epithelial homeostasis or possibly non-transcriptomic factors.

Castleman Disease of the Thorax: Clinical, Radiologic, and Pathologic Correlation: From the Radiologic Pathology Archives.

Castleman disease is a complex lymphoproliferative disease pathologically divided into two subtypes, the hyaline vascular variant (HVV) and the plasma cell variant (PCV). The HVV is the most common, is thought to represent a benign neoplasm of lymph node stromal cells, and is treated with surgical resection. It is most commonly found in the mediastinum, where it classically appears as a unicentric, avidly enhancing mass at computed tomography (CT) and magnetic resonance imaging. This appearance can mimic other avidly enhancing mediastinal masses, and location, clinical history, laboratory data, and nuclear medicine single photon emission CT (SPECT) and positron emission tomography (PET) studies can help narrow the differential diagnosis. Multicentric Castleman disease (MCD), which in the majority of cases is composed of the PCV, is an aggressive lymphoproliferative disorder associated with human herpesvirus infection, interleukin 6 dysregulation, and other systemic disorders. While it can be difficult to differentiate MCD from lymphoma, the presence of avidly enhancing lymph nodes can suggest the diagnosis. The purpose of this article is to review the clinical, immunologic, and pathologic findings associated with both unicentric Castleman disease and MCD and discuss how the imaging findings correlate with the pathophysiology of the disease.

Primary Pulmonary Lymphoid Lesions: Radiologic and Pathologic Findings.

The pulmonary lymphoid system is complex and is composed of two compartments: the pulmonary lymphatics and the bronchus-associated lymphoid tissue (BALT). Additional important cells that function in the pulmonary lymphoid system include dendritic cells, Langherhans cells, macrophages, and plasma cells. An appreciation of the normal lymphoid anatomy of the lung as well as its immunology is helpful in understanding the radiologic and pathologic findings of the primary pulmonary lymphoid lesions. Primary lymphoid lesions of the lung arise from the BALT and are uncommon. However, they are increasingly recognized within the growing number of posttransplant patients as well as other patients who are receiving immunosuppressive therapies. Primary lymphoid lesions encompass a wide range of benign and malignant lesions. Benign lymphoid lesions of the lung include reactive lymphoid hyperplasia, follicular bronchiolitis, lymphoid interstitial pneumonia, and nodular lymphoid hyperplasia. Malignant lymphoid lesions of the lung include low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT), other non-Hodgkin lymphomas, and Hodgkin lymphoma. Last, a miscellaneous group of primary lymphoid lesions includes lymphomatoid granulomatosis, posttransplant lymphoproliferative disorders, acquired immunodeficiency syndrome (AIDS)-related lymphoma, and intravascular lymphoma/lymphomatosis. These lesions are best evaluated with multidetector chest computed tomography. The radiologic findings of the primary lymphoid lesions are often nonspecific and are best interpreted in correlation with clinical data and pathologic findings. The purpose of this article is to review pulmonary lymphoid anatomy as well as the most common primary pulmonary lymphoid disorders.

CT-Definable Subtypes of Chronic Obstructive Pulmonary Disease: A Statement of the Fleischner Society.

The purpose of this statement is to describe and define the phenotypic abnormalities that can be identified on visual and quantitative evaluation of computed tomographic (CT) images in subjects with chronic obstructive pulmonary disease (COPD), with the goal of contributing to a personalized approach to the treatment of patients with COPD. Quantitative CT is useful for identifying and sequentially evaluating the extent of emphysematous lung destruction, changes in airway walls, and expiratory air trapping. However, visual assessment of CT scans remains important to describe patterns of altered lung structure in COPD. The classification system proposed and illustrated in this article provides a structured approach to visual and quantitative assessment of COPD. Emphysema is classified as centrilobular (subclassified as trace, mild, moderate, confluent, and advanced destructive emphysema), panlobular, and paraseptal (subclassified as mild or substantial). Additional important visual features include airway wall thickening, inflammatory small airways disease, tracheal abnormalities, interstitial lung abnormalities, pulmonary arterial enlargement, and bronchiectasis.

Mosaic Attenuation: Etiology, Methods of Differentiation, and Pitfalls.

Mosaic attenuation is a commonly encountered pattern on computed tomography that is defined as heterogeneous areas of differing lung attenuation. This heterogeneous pattern of attenuation is the result of diverse causes that include diseases of the small airways, pulmonary vasculature, alveoli, and interstitium, alone or in combination. Small airways disease can be a primary disorder, such as respiratory bronchiolitis or constrictive bronchiolitis, or be part of parenchymal lung disease, such as hypersensitivity pneumonitis, or large airways disease, such as bronchiectasis and asthma. Vascular causes resulting in mosaic attenuation are typically chronic thromboembolic pulmonary hypertension, which is characterized by organizing thrombi in the elastic pulmonary arteries, or pulmonary arterial hypertension, a heterogeneous group of diseases affecting the distal pulmonary arterioles. Diffuse ground-glass opacity can result in a mosaic pattern related to a number of processes in acute (eg, infection, pulmonary edema), subacute (eg, organizing pneumonia), or chronic (eg, fibrotic diseases) settings. Imaging clues that can assist the radiologist in pinpointing a diagnosis include evidence of large airway involvement, cardiovascular abnormalities, septal thickening, signs of fibrosis, and demonstration of airtrapping at expiratory imaging.

Missed pulmonary emboli on CT angiography: assessment with pulmonary embolism-computer-aided detection.

OBJECTIVE: The purpose of this study is to assess the use of a pulmonary embolism (PE)- computer-aided detection (CADx) program in the detection of PE missed in clinical practice. MATERIALS AND METHODS: Pulmonary CT angiography (CTA) studies (n = 6769) performed between January 2009 and July 2012 were retrospectively assessed by a thoracic radiologist. In studies that were positive for PE, all prior contrast-enhanced pulmonary CTA studies were reviewed. Missed PE was deemed to have occurred if PE was not described in the final interpretation. The presence, proximal extent, and number of PEs were agreed on by three thoracic radiologists. Studies with missed acute PE and available slice thickness of 2 mm or less were assessed with a prototype PE-CADx program. False-positive PE-CADx marks were analyzed. Outcomes of missed acute PEs were assessed in patients with both follow-up imaging and clinical data. RESULTS: Fifty-three studies with overlooked acute PE met our inclusion criteria for PE-CADx assessment. The PE-CADx program identified at least one PE in 77.4% of instances (41/53). PE-CADx correctly marked at least one PE in 23 of 23 cases (100%) with multiple PEs and 18 of 30 (60%) cases with a solitary PE (p < 0.001). PE-CADx per-study sensitivity was significantly higher for segmental (65.5%) than for subsegmental (91.7%) PEs (p = 0.002). PE-CADx averaged 3.8 false-positive marks per case (range, 0-23 marks). Fourteen patients with missed PE who were not receiving anticoagulation therapy developed new PEs, including nine with an isolated subsegmental PE on the initial CT scan. CONCLUSION: PE-CADx correctly identified 77.4% of cases of acute PE that were previously missed in clinical practice.

From the radiologic pathology archives: organization and fibrosis as a response to lung injury in diffuse alveolar damage, organizing pneumonia, and acute fibrinous and organizing pneumonia.

Organization, characterized by fibroblast proliferation, is a common and nearly universal response to lung injury whether it is focal or diffuse. Despite the vast range of injurious agents, the lung's response to injury is quite limited, with a similar pattern of reaction seen radiologically and histologically regardless of the underlying cause. Although there is a tendency to divide organization into distinct entities, the underlying injury to the alveolar epithelial basement membrane is a uniting factor in these processes. This pattern of lung injury is seen in the organizing phase of diffuse alveolar damage, organizing pneumonia (OP), acute fibrinous and organizing pneumonia, and certain types of fibrotic lung disease. In addition, although organization can heal without significant injury, in some instances it progresses to fibrosis, which can be severe. When fibrosis due to organization is present, other histologic and imaging patterns, such as those seen in nonspecific interstitial pneumonia, can develop, reflecting that fibrosis can be a sequela of organization. This article reviews the histologic and radiologic findings of organization in lung injury due to diffuse alveolar damage, OP, and acute fibrinous and organizing pneumonia and helps radiologists understand that the histologic and radiologic findings depend on the degree of injury and the subsequent healing response.

Consensus Statements on Deployment-Related Respiratory Disease, Inclusive of Constrictive Bronchiolitis: A Modified Delphi Study.

BACKGROUND: The diagnosis of constrictive bronchiolitis (CB) in previously deployed individuals, and evaluation of respiratory symptoms more broadly, presents considerable challenges, including using consistent histopathologic criteria and clinical assessments. RESEARCH QUESTION: What are the recommended diagnostic workup and associated terminology of respiratory symptoms in previously deployed individuals? STUDY DESIGN AND METHODS: Nineteen experts participated in a three-round modified Delphi study, ranking their level of agreement for each statement with an a priori definition of consensus. Additionally, rank-order voting on the recommended diagnostic approach and terminology was performed. RESULTS: Twenty-five of 28 statements reached consensus, including the definition of CB as a histologic pattern of lung injury that occurs in some previously deployed individuals while recognizing the importance of considering alternative diagnoses. Consensus statements also identified a diagnostic approach for the previously deployed individual with respiratory symptoms, distinguishing assessments best performed at a local or specialty referral center. Also, deployment-related respiratory disease (DRRD) was proposed as a broad term to subsume a wide range of potential syndromes and conditions identified through noninvasive evaluation or when surgical lung biopsy reveals evidence of multicompartmental lung injury that may include CB. INTERPRETATION: Using a modified Delphi technique, consensus statements provide a clinical approach to possible CB in previously deployed individuals. Use of DRRD provides a broad descriptor encompassing a range of postdeployment respiratory findings. Additional follow-up of individuals with DRRD is needed to assess disease progression and to define other features of its natural history, which could inform physicians better and lead to evolution in this nosology.

From the radiologic pathology archives: cardiac lymphoma: radiologic-pathologic correlation.

Lymphoma of the heart and pericardium is usually present as one aspect of disseminated disease and rarely occurs as a primary malignancy. It accounts for 1.3% of primary cardiac tumors and 0.5% of extranodal lymphomas. Cardiac lymphomas are most commonly diffuse large cell lymphomas and frequently manifest as an ill-defined, infiltrative mass. Atrial location is typical; the right atrium is most often affected. Pericardial thickening or effusion is often a common early feature of disease. Infiltration of atrial or ventricular walls with extension along epicardial surfaces is also a notable feature. At computed tomography, the attenuation of cardiac lymphoma may be similar to or lower than that of normal myocardium. At magnetic resonance imaging, it has variable signal intensity and contrast enhancement. Clinical manifestations may include pericardial effusion, cardiac arrhythmias, and a variety of nonspecific electrocardiographic abnormalities, notably first- to third-degree atrioventricular block. Treatment most commonly includes anthracycline-based chemotherapy and anti-CD20 treatment. Chemotherapy has been used alone or combined with radiation therapy. Palliative surgery has been performed, mainly for tumor debulking. The prognosis for patients with either primary or secondary lymphomatous heart involvement is usually poor; late diagnosis is one of the major factors affecting outcome.

Mosaic Attenuation Pattern: A Guide to Analysis with HRCT.

Mosaic attenuation pattern is commonly encountered on high-resolution computed tomography and has myriad causes. These diseases may involve small airways, vessels, alveoli, or interstitium, with some involving compartmental combinations. Small airways disease is caused by cellular bronchiolitis, infiltrated by inflammatory cells or constrictive bronchiolitis, resulting in fibrosis of the small airways. Any acute or chronic cause of ground-glass opacity can result in a mosaic pattern. Vascular causes of mosaic attenuation include chronic thromboembolic pulmonary hypertension and rarely other causes of pulmonary arterial hypertension. Ancillary CT findings along with the clinical history help narrow the differential diangosis. Biopsy is uncommonly required for definitiive diagnosis.

Demystifying idiopathic interstitial pneumonia: time for more etiology-focused nomenclature in interstitial lung disease.

INTRODUCTION: A major focus of interstitial lung disease (ILD) has centered on disorders termed idiopathic interstitial pneumonias (IIPs) which include, among others, idiopathic pulmonary fibrosis, idiopathic nonspecific interstitial pneumonia, cryptogenic organizing pneumonia, and respiratory bronchiolitis-interstitial lung disease. AREAS COVERED: We review the radiologic and histologic patterns for the nine disorders classified by multidisciplinary approach as IIP, and describe the remarkable amount of published epidemiologic, translational, and molecular studies demonstrating their associations with numerous yet definitive environmental exposures, occupational exposures, pulmonary diseases, systemic diseases, medication toxicities, and genetic variants. EXPERT OPINION: In the 21st century, these disorders termed IIPs are rarely idiopathic, but rather are well-described radiologic and histologic patterns of lung injury that are associated with a wide array of diverse etiologies. Accordingly, the idiopathic nomenclature is misleading and confusing, and may also promote a lack of inquisitiveness, suggesting the end rather than the beginning of a thorough diagnostic process to identify ILD etiology and initiate patient-centered management. A shift toward more etiology-focused nomenclature will be beneficial to all, including patients hoping for better life quality and disease outcome, general medicine and pulmonary physicians furthering their ILD knowledge, and expert ILD clinicians and researchers who are advancing the ILD field.

Autologous Stem Cell Transplantation in the Treatment of Pulmonary Light Chain Deposition Disease.

Light chain deposition disease is a rare condition that results in the deposition of light chains in organs and their subsequent dysfunction. It is often the consequence of unchecked light chain production by a plasma cell clone. Rarely does it manifest with solely pulmonary involvement, especially in the young otherwise healthy patient. This article highlights the presentation and diagnosis of pulmonary light chain deposition disease in an active duty solider, the discovery of a plasma cell clone responsible for his symptoms, and the therapy targeted at the plasma cell clone-inducing pulmonary disease. This therapy included a novel successful treatment with an autologous stem cell transplantation. To date, it is among the first such documented successful bone marrow transplantations in treatment of isolated pulmonary light chain deposition disease.

Non-Infectious Granulomatous Lung Disease: Imaging Findings with Pathologic Correlation.

Non-infectious granulomatous lung disease represents a diverse group of disorders characterized by pulmonary opacities associated with granulomatous inflammation, a relatively nonspecific finding commonly encountered by pathologists. Some lesions may present a diagnostic challenge because of nonspecific imaging features; however, recognition of the various imaging manifestations of these disorders in conjunction with patients' clinical history, such as age, symptom onset and duration, immune status, and presence of asthma or cutaneous lesions, is imperative for narrowing the differential diagnosis and determining appropriate management of this rare group of disorders. In this pictorial review, we describe the pathologic findings of various non-infectious granulomatous lung diseases as well as the radiologic features and high-resolution computed tomography imaging features.

A comprehensive assessment of environmental exposures and the medical history guides multidisciplinary discussion in interstitial lung disease.

BACKGROUND: Multidisciplinary discussion (MDD) is widely recommended for patients with interstitial lung disease (ILD), but published primary data from MDD has been scarce, and factors influencing MDD other than chest computed tomography (CT) and lung histopathology interpretations have not been well-described. METHODS: Single institution MDD of 179 patients with ILD. RESULTS: MDD consensus clinical diagnoses included autoimmune-related ILD, chronic hypersensitivity pneumonitis, smoking-related ILD, idiopathic pulmonary fibrosis, medication-induced ILD, occupation-related ILD, unclassifiable ILD, and a few less common pulmonary disorders. In 168 of 179 patients, one or more environmental exposures or pertinent features of the medical history were identified, including recreational/avocational, residential, and occupational exposures, systemic autoimmune disease, malignancy, medication use, and family history. The MDD process demonstrated the importance of comprehensively assessing these exposures and features, beyond merely noting their presence, for rendering consensus clinical diagnoses. Precise, well-defined chest CT and lung histopathology interpretations were rendered at MDD, including usual interstitial pneumonia, nonspecific interstitial pneumonia, and organizing pneumonia, but these interpretations were associated with a variety of MDD consensus clinical diagnoses, demonstrating their nonspecific nature in many instances. In 77 patients in which MDD consensus diagnosis differed from referring diagnosis, assessment of environmental exposures and medical history was found retrospectively to be the most impactful factor. CONCLUSIONS: A comprehensive assessment of environmental exposures and pertinent features of the medical history guided MDD. In addition to rendering consensus clinical diagnoses, MDD presented clinicians with opportunities to initiate environmental remediation, behavior modification, or medication alteration likely to benefit individual patients with ILD.

Collaborative radiologic and histopathologic assessment of fibrotic lung disease.

The idiopathic interstitial pneumonias (IIPs) are a seemingly disconnected collection of diseases usually associated with the presence of pulmonary fibrosis. Categorization of the IIPs continues to be problematic despite recent attempts to refine the diagnostic criteria and suggests that rather than separate diseases, these pneumonias represent a spectrum of injury and abnormal repair of the alveolar wall. Although the initiating injury or injuries are unknown, the IIPs share a restricted number of final common abnormal pathways that lead to volume loss and lung distortion. The pathways include (a) alveolar collapse, (b) incorporation of fibroblastic material into alveolar walls, and (c) cigarette smoke-related inflammation and fibrosis. A collaborative diagnostic process in which data from radiologic and histologic assessments are combined allows a more reliable identification of the predominant pathways leading to pulmonary fibrosis. This approach has implications for therapy and the future direction of research.

Complex obstructive lung disease - A diagnostic and management conundrum.

Rheumatoid arthritis (RA) is a common autoimmune disease most well-known for its inflammatory, destructive polyarthropathy. Extraarticular manifestations of the disease may involve the respiratory system, including interstitial lung disease, pleural disease, pulmonary vascular abnormalities, and airways disease. Smoking is highly prevalent in the RA population, and may even have a synergistic effect in disease development and progression. In the diagnosis of pulmonary disease, this presents a unique diagnostic and therapeutic challenge. We present a case of a woman in her 50s who presented for evaluation of dyspnea and was found to have obstructive lung disease. In addition to RA, she had a significant smoking history and also owned pet birds, making definitive diagnosis difficult. Ultimately, chest imaging was crucial in identifying RA-related lung disease as the root cause of her symptoms, leading to successful treatment and symptom management.

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.