CT findings of lung injury during breast cancer treatment

Pictorial Essay: Multinodular Disease

Strong Association between Respiratory Viral Infection Early after Hematopoietic Stem Cell Transplantation and the Development of Life-Threatening Acute and Chronic Alloimmune Lung Syndromes

Background: BOOP is an inflammatory pulmonary disorder consisting of organized polypoid granulation tissue in the distal airways extending into the alveolar ducts and alveoli. Clinical manifestations of BOOP include fever, cough, dyspnea on exertion, and fatigue. Patients with severe BOOP require hospitalization. The mainstay of BOOP treatment is high dose corticosteroids. Many patients relapse and require long term corticosteroids, often in combination with another immunosuppressant. Significant morbidity and disability may be associated with both the diagnosis of BOOP and the toxicities of treatment. The mortality rate of BOOP has been estimated to be about 5%. Radiation Therapy (RT) is an important component in the treatment of breast cancer (Breast Ca). Beginning in 1995, reports of BOOP occurring in Breast Ca RT patients began to appear in the medical literature. From 1995 to the present, 43 case study reports described 121 Breast Ca RT patients who developed BOOP within one year of their RT. From 1999 to 2011, seven epidemiological studies were published that suggested that the incidence of BOOP in Breast Ca RT patients was in the range of 2% to 3%. Objectives: The primary objective of this study was to determine if internet sources of Breast Ca information targeted to Breast Ca patients include BOOP information in their description of RT risks. The secondary objective was to determine if general medical websites conveyed BOOP/Breast Ca RT risk information. Methods: Eight websites specifically targeted to Breast Ca patients were reviewed. Sponsors of these websites included the US government, Breast Ca advocacy groups, and medical organizations. Seven general medical websites that contained BOOP/Breast Ca RT information were also reviewed. Results: There was no mention of BOOP in any of the websites targeted to Breast Ca patients. The websites included those from the National Cancer Institute, American Cancer Society, American Society of Therapeutic Radiology and Oncology, Susan G. Komen, and BreastCancer.org. The internet search identified seven general medical websites that did include information about the risk of BOOP from Breast Ca RT. Discussion: It is perplexing that none of the eight website sources for Breast Ca patients included any mention of the risk of BOOP associated with Breast Ca RT, whereas seven general medical internet sources did disclose this information. This disparity raises important issues and questions. The majority of BOOP/Breast Ca RT reports were published in pulmonology journals. Is this information being disseminated to providers of Breast Ca treatment? Many of the Breast Ca information websites stated that their information was up to date and was reviewed by leading Breast Ca physicians, so it remains an enigma that the BOOP/RT association was not disclosed. The lack of any information about BOOP and Breast Ca RT may indicate Breast Ca physician unawareness. An alternative explanation for this finding may be that these physicans are aware of the BOOP/RT association, but they believe that the rarity of BOOP diagnoses justifies omitting this information in internet-based information sources. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-11-02.

816 Background: The aim of the study was to evaluate late myocardial and pulmonary damage in breast cancer patients, after mastectomy and adjuvant sequential chemo-radiotherapy. Methods: Forty seven women with stage II and III breast cancer had mastectomy and sequential chemo-radiotherapy. In 40 patients (pts) chemotherapy with antracyclines and in 7- without antracyclines was administered. Radiotherapy included chest wall and regional lymph nodes, the specified dose was 45–50Gy /2 Gy. The high resolution computed tomography (HRCT) of the lungs, electrocardiography and echocardiography were performed after a mean time of 17 months, then, after a mean time of 33 months and finally, after a mean time of 65 months. Results: LUNGS-The first examination (after 17 monts) revealed no changes in 24 pts (51%). There were fibrotic changes in lung apex in 19 pts and 19 parietal fibrosis. In the second examination (after 33 months) a tendency to regression in parietal areas was observed (p=0.031). In third examination (after 65 months), the same percentage of pts −51% had no lung injury. The lung fibrosis was observed in 14 and parietal- in 13 pts.All these changes were discrete and asymptomatic and parietal fibrosis were invisible in chest X-ray. HEART- In first examination 7 of 47 pts had abnormal echocardiogram (ventricular dilatation, abnormal Left Ventricular Ejection Fraction). All of them received antracyclines. In 5 of them echocardiografic defect were asymptomatic and reversible at the time of second examination, in 2 -moderate toxicity was noted. The analysis of isodose distribution in all 7 cases excluded radiotherapy as a factor influencing toxicity. After 65 months, no new cardiac complications were observed and the improvement in echocardiography in 6 patients was observed (1 patient died because of disseminated disease). Conclusions: Modern postoperative radiotherapy caused no clinically significant lesions in lung and heart during 5 years of observation. Clinically important, reversible, myocardial changes, observed in 2 pts, seemed to be caused by antracyclines, but not by radiotherapy. No significant financial relationships to disclose.

Optimizing the utility of high-resolution computed tomography in diagnosing cryptogenic organizing pneumonia

The degree of normal fibroglandular tissue that enhances on breast MRI, known as background parenchymal enhancement (BPE), was initially described as an incidental finding that could affect interpretation performance. While BPE is now established to be a physiologic phenomenon that is affected by both endogenous and exogenous hormone levels, evidence supporting the notion that BPE frequently masks breast cancers is limited. However, compelling data have emerged to suggest BPE is an independent marker of breast cancer risk and breast cancer treatment outcomes. Specifically, multiple studies have shown that elevated BPE levels, measured qualitatively or quantitatively, are associated with a greater risk of developing breast cancer. Evidence also suggests that BPE could be a predictor of neoadjuvant breast cancer treatment response and overall breast cancer treatment outcomes. These discoveries come at a time when breast cancer screening and treatment have moved toward an increased emphasis on targeted and individualized approaches, of which the identification of imaging features that can predict cancer diagnosis and treatment response is an increasingly recognized component. Historically, researchers have primarily studied quantitative tumor imaging features in pursuit of clinically useful biomarkers. However, the need to segment less well-defined areas of normal tissue for quantitative BPE measurements presents its own unique challenges. Furthermore, there is no consensus on the optimal timing on dynamic contrast-enhanced MRI for BPE quantitation. This article comprehensively reviews BPE with a particular focus on its potential to increase precision approaches to breast cancer risk assessment, diagnosis, and treatment. It also describes areas of needed future research, such as the applicability of BPE to women at average risk, the biological underpinnings of BPE, and the standardization of BPE characterization. Level of Evidence: 3 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2020;51:43-61.

A SEVERE CASE OF ORGANIZING PNEUMONIA FROM VAPING AND COCAINE USE

We conducted a review of serial high-resolution CT (HRCT) findings of cryptogenic organizing pneumonia (COP). Over the course of 14 years, we saw 32 patients with biopsy-confirmed COP. Serial HRCT scans were available for only 22 patients (seven men and 15 women; mean age, 52 years; median follow-up period, 8 months; range, 5-135 months). Serial CT scans were evaluated by two chest radiologists who reached a conclusion by consensus. Overall changes in disease extent were classified as cured, improved (i.e., ≥ 10% decrease in extent), not changed, or progressed (i.e., ≥ 10% increase in extent). When there were remaining abnormalities, the final follow-up CT images were analyzed to express observers' ideas regarding what type of interstitial lung disease the images most likely suggested. The two most common patterns of lung abnormality on initial scans were ground-glass opacification (86% of patients [19/22]) and consolidation (77% of patients [17/22]), distributed along the bronchovascular bundles or subpleural lungs in 13 patients (59%). In six patients (27%), the disease disappeared completely; in 15 patients (68%), the disease was decreased in extent; and in one patient (5%), no change in extent was detected on follow-up CT. When lesions remained, the final follow-up CT findings were reminiscent of fibrotic nonspecific interstitial pneumonia in 10 of 16 patients (63%). Although COP is a disease with a generally good prognosis, most patients (73%) with COP have some remaining disease seen on follow-up CT scans, and, in such cases, the lesions generally resemble a fibrotic nonspecific interstitial pneumonia pattern.

Diffuse alveolar damage (DAD), which represents the pathologic changes seen after acute lung injury, is caused by damage to all three layers of the alveolar wall and can ultimately result in alveolar collapse with loss of the normal pulmonary architecture. DAD has an acute phase that predominantly manifests as airspace disease at CT owing to filling of the alveoli with cells, plasma fluids, and hyaline membranes. DAD then evolves into a heterogeneous organizing phase, with mixed airspace and interstitial disease characterized by volume loss, architectural distortion, fibrosis, and parenchymal loss. Patients with DAD have a severe clinical course and typically require prolonged mechanical ventilation, which may result in ventilator-induced lung injury. In those patients who survive DAD, the lungs will remodel over time, but most will have residual findings at chest CT. Organizing pneumonia (OP) is a descriptive term for a histologic pattern characterized by intra-alveolar fibroblast plugs. The significance and pathogenesis of OP are controversial. Some authors regard it as part of a spectrum of acute lung injury, while others consider it a marker of acute or subacute lung injury. At CT, OP manifests with various forms of airspace disease that are most commonly bilateral and relatively homogeneous in appearance at individual time points. Patients with OP most often have a mild clinical course, although some may have residual findings at CT. In patients with DAD and OP, imaging findings can be combined with clinical information to suggest the diagnosis in many cases, with biopsy reserved for difficult cases with atypical findings or clinical manifestations. To best participate in the multidisciplinary approach to patients with lung injury, radiologists must not only recognize these entities but also describe them with consistent and meaningful terminology, examples of which are emphasized in the article. © RSNA, 2023 See the invited commentary by Kligerman et al in this issue. Quiz questions for this article are available in the supplemental material.

Recently, exhaled nitric oxide (eNO) was recognized as a noninvasive marker of lung inflammation (1). Bronchiolitis obliterans organizing pneumonia (BOOP) is characterized by a histologic finding of bronchiolitis with granulation tissue in small airways, in alveolar ducts and some alveoli, and in the area of organizing pneumonia (2). Idiopathic BOOP after allogeneic bone marrow transplantation (BMT) is thought to be a noninfectious lung complication and an association of chronic graft-versus-host disease (GVHD), although the etiology is still unknown. We found increased eNO concentration and improvement with immunosuppressive therapy in three patients in whom idiopathic BOOP developed after allogeneic BMT. The time course of eNO levels after the onset of BOOP is shown in Figure 1.Figure 1: Time course of eNO levels after treatment with prednisolone for BOOP. Exhaled NO level was measured according to the recommendation of the European Respiratory Society (9), with a minor modification; exhalation flow rate of 60 mL/sec.Case 1. A 19-year-old male with chronic myelogenous leukemia received a BMT from his HLA-identical sister in November 1997. The conditioning regimen consisted of fractionated total body irradiation (TBI), etoposide, and cyclophosphamide (CY). Short-term methotrexate and cyclosporine were given to prevent GVHD. Engraftment of bone marrow was favorable. After tapering of cyclosporine, the patient complained of nonproductive cough and low-grade fever on day 150. Chest radiograph revealed multiple patchy infiltrates with air bronchogram. High-resolution computed tomography (CT) of the lung demonstrated bilateral nodular patchy inclusions. Lung function tests showed a moderately restrictive impairment. Transbronchial lung biopsy (TBLB) and bronchoalveolar lavage (BAL) were performed on day 245. Pathologic findings showed typical features of BOOP. Cytology of BAL fluid revealed a high lymphocyte count (36.0%). Examination of BAL fluid for bacteria, fungi, Pneumocystis, and viruses including cytomegalovirus was negative. The eNO level was 51 parts per billion (ppb) (normal control is 12.9±3.8 [SD] ppb) at the onset of BOOP. He received prednisolone (PSL) at a dose of 1 mg/kg daily. Clinical symptoms disappeared, and the lung lesion mainly improved on CT scan within a month. The eNO level decreased to 13 ppb on day 288. Case 2. A 39-year-old male with chronic myelogenous leukemia underwent a BMT from his HLA-matched sister in November 1998. Conditioning consisted of TBI, cytarabine, and CY. GVHD prophylaxis was identical to case 1. He developed chronic GVHD and has been treated with 10 mg of PSL. He complained of dyspnea and fever on day 667. The results of CT of the lung and TBLB were compatible with BOOP. The cytology of BAL fluid indicated an eosinophil count of 6% and lymphocyte count of 7%. The eNO level showed 52 ppb on day 681. After 1 mg/kg PSL was given, the level of eNO improved to the normal range, with disappearance of clinical findings. Case 3. A 43-year-old male with acute myelogenous leukemia in remission received an HLA-matched unrelated donor BMT in September 2000. The conditioning with TBI and thiotepa and the CY and GVHD prophylaxis was the same as in the above cases. BOOP developed on day 144. The findings of CT scan and TBLB were consistent with BOOP. The BAL fluid indicated a lymphocytosis of 85%. The eNO slightly increased to 18 ppb at this point. He had two recurrences of BOOP, despite treatment with PSL. The level of eNO was 36 ppb at the second recurrence on day 336. After administration of high-dose methyl prednisolone, BOOP was improved, with normalization of eNO level. NO is synthesized from l-arginine in many cells of the respiratory tract by NO synthases. Inducible NO synthase is especially capable of producing large amounts of NO in response to proinflammatory cytokines such as interleukin 1 and tumor necrosis factor-α (3). In a murine BMT model of idiopathic pulmonary syndrome, it has been described that alloreactive T cells activate host alveolar macrophages to release NO and increased NO levels are associated with lung dysfunction (4). BMT-related BOOP usually develops as a late-onset noninfectious pulmonary complication and is often connected with chronic GVHD (5). Therefore, it is speculated that an immune-mediated mechanism and tissue-damaging NO may contribute to the onset and clinical future of BOOP. In previous studies, a significant correlation has been observed between the levels of serum nitrite/nitrate and host-versus-graft and graft-versus-host reactions in rat (6) and human (7,8) BMT. In consideration of these findings, increased eNO production in our cases also suggests that BMT-related BOOP may be a manifestation of chronic GVHD. Although the pathogenesis of BOOP is probably multifactorial and the physiologic role of NO in this pulmonary complication should be resolved, we believe the eNO measurement is a useful monitor for an inflammatory complication such as BOOP after BMT. Heiwa Kanamori1 2 Shin Fujisawa1 Takahiro Tsuburai1 Satoshi Yamaji1 Naoto Tomita1 Katsumichi Fujimaki1 Akira Miyashita1 Shunsuke Suzuki1 Yoshiaki Ishigatsubo1

High Resolution Computed Tomography of Bleomycin-Induced Lung Injury in Hodgkin Lymphoma.

To analyze the high-resolution computed tomographic (HRCT) findings of IPF (interstitial pulmonary fibrosis), NSIP (nonspecific interstitial pneumonia) and COP (cryptogenic organizing pneumonia) retrospectively through quantification methods and to explore their distinguishing features. Observers with no prior knowledge of the diagnosis evaluated the frequency, extent and distribution of various thin-section CT findings in 29 males and 17 females. The mean age was 50 ± 10 years old (range: 25 - 76). They had a histological diagnosis of IPF (n = 19), nonspecific interstitial pneumonia (NSIP) (n = 14) and cryptogenic organizing pneumonia (COP) (n = 13). Ground-glass opacity, thickening of bronchovascular bundles and interlobular septal thickening were frequent features of IPF and NSIP. The frequency and extent of honeycombing and bronchiolectasis were more found in IPF than in NSIP and COP (P < 0.05). The frequency and extent of air space consolidation were more found in COP than IPF (P < 0.05). There were more number of segments with traction bronchiectasis and less extent of air space consolidation in IPF than NSIP and COP. The number of segments with traction bronchiectasis was less in NSIP than that of IPF and COP. The various subtypes of idiopathic interstitial pneumonias often have the distinguishing characteristics easily identified on HRCT. Bronchiolectasis and honeycombing are valuable features for IPF; air space consolidation is a valuable feature for COP. The features of NSIP are also found in both IPF and COP so that additional features are required for both.

Background The peri-bronchovascular interstitium is a system of fibers that surrounds the bronchi and pulmonary arteries. Infection is the most common peri-bronchovascular pathology. Other frequent diseases target the peri-bronchovascular interstitium and express a predilection for lymphatic routes including sarcoid disease, lymphoproliferative disorders, lymphangitis carcinomatosis, and rarely occupational lung diseases. Other pathologies that target the peri-bronchovascular interstitium lacking a peri-lymphatic distribution include cryptogenic organizing pneumonia (COP) and rarely Kaposi’s sarcoma. Aim of the work To achieve a multidisciplinary approach collaborating certain clinical features, laboratory data, and CT findings that can narrow the differential diagnosis of peri-bronchovascular lung diseases to avoid the hazards of lung biopsy. Results This study was planned to include two major steps; the first step included a retrospective prevalence analysis regarding the clinical, radiological, laboratory, and pathological parameters of peri-bronchovascular lung diseases; this included 200 patients during the period from July 2022 to June 2024. The study was performed by three expert consulting radiologists and a single consulting pulmonologist in consensus. Diseases with acute onset were concluded in 51% of patients with either infection, cardiogenic pulmonary edema, or pulmonary alveolar hemorrhage. Diseases with chronic lung fibrosis were concluded in 24% of patients with either progressive massive fibrosis, stage IV sarcoidosis, NSIP, or chronic hypersensitivity pneumonitis. Non-fibrotic diseases with parenchymal CT findings alone were concluded in 15% of patients with either sarcoidosis (stage III), cryptogenic organizing pneumonia (COP), chronic eosinophilic pneumonia (CEP), Wagner granulomatosis, adenocarcinoma, lymphoma, or leukemia. Non-fibrotic diseases with additional extra-parenchymal CT findings were concluded in 10% of patients with either sarcoidosis, lymphoma, leukemia, adenocarcinoma, or Wegner granulomatosis. Statistically significant parameters with P value &lt; 0.05 were used to achieve a diagnostic approach. The second step of this study prospectively included 50 patients with peri-bronchovascular lesions from July 2024 to January 2025 who were subjected to the proposed diagnostic approach. It was proved to be valid by reaching 92–100% sensitivity, 84–99% specificity, 84–98% positive predictive value (PPV), 93–100% negative predictive value (NPV), and 91–99% accuracy. Conclusions A valid multidisciplinary approach is currently proposed for diagnosing peri-bronchovascular lung diseases combining their clinical, HRCT, laboratory, and pathological parameters.

The aim of this study was to report the high-resolution computed tomography (HRCT) appearances of linear opacities that may occur in isolation or in combination with other changes in bronchiolitis obliterans organising pneumonia (BOOP). Eleven patients with BOOP and linear opacities on HRCT were identified at three independent teaching hospitals. The HRCT images and clinical course of each patient were reviewed. Two distinct types of linear opacity were identified. The type-1 opacity extended in a radial manner along the line of the bronchi towards the pleura and was usually intimately related to bronchi. The type-2 opacity occurred in a sub-pleural location and bore no relationship to the bronchi. Both types occurred most commonly in the lower lobes, frequently were associated with multi-focal areas of consolidation and usually completely resolved with treatment. There was no associated bronchiectasis, irreversible volume loss or a reticular or honeycomb pattern. In 2 patients linear opacities were the sole abnormality on HRCT. Bronchiolitis obliterans organising pneumonia may occur in a pure "linear form" or HRCT may demonstrate linear opacities in addition to multi-focal consolidation.

This study compared the results of high-resolution computed tomography (HRCT) and cytohistology after transbronchial biopsy in the evaluation of drug-related interstitial lung disease (DR-ILD). Patients with a clinical and imaging diagnosis of DR-ILD were prospectively included in a study protocol lasting 5 years. All patients were evaluated by bronchoscopy with transbronchial biopsy or bronchoalveolar lavage (BAL) following an HRCT examination that raised a suspicion of DR-ILD. Two radiologists (one senior and one junior), unaware of the diagnosis, reported the single HRCT findings, their distribution and predominant pattern. In the event of disagreement, the diagnosis was subsequently reached by consensus. Cytohistological examination was considered the gold standard in the diagnosis of DR-ILD. Patients who were unable to undergo the endoscopic procedure were excluded from the study. The study included 42 patients (25 men, 17 women; age range 20-84 years). Transbronchial biopsy was performed in all but four patients (one case of alveolar haemorrhage and three cases of lipoid pneumonia) in whom the diagnosis was established with BAL. Assessment of the HRCT images revealed the following patterns: noncardiogenic pulmonary oedema (n=13); organising pneumonia (OP) (n=9); hypersensitivity pneumonitis (HP) (n=2); alveolar haemorrhage (AH) (n=2); nonspecific interstitial pneumonia (NSIP) (n=5); lipoid pneumonia (LP) (n=1); sarcoid-like pattern (n=1). Cytohistological diagnosis revealed diffuse alveolar damage (DAD) in 11 patients, OP in seven, HP in three, AH in three, chronic interstitial pneumonia (CIP) in eight, LP in three and pseudosarcoidosis in one. Subdivision of the drugs into antineoplastic and nonantineoplastic agents showed that the most common patterns were CIP (n=6), DAD (n=2) and OP (n=2) in the antineoplastic group and DAD (n=9) and OP (n=5) in the nonantineoplastic group. Sensitivity and specificity of the radiological analysis was excellent, especially for patterns such as OP and DAD (sensitivity 0.86 and specificity 0.88 for OP; sensitivity 1 and specificity 0.93 for DAD). HRCT demonstrated excellent sensitivity and specificity. In cases in which its specificity was low, HRCT was nonetheless useful for biopsy planning and clinical-radiological monitoring after discontinuation of the drug treatment.