Pulmonary Drug Toxicity: Radiologic and Pathologic Manifestations1
Santiago E. Rossi, MD,
Jeremy J. Erasmus, MD,
H. Page McAdams, MD,
Thomas A. Sporn, MD and
Philip C. Goodman, MD
1 From the Departments of Radiology (S.E.R., J.J.E., H.P.M., P.C.G.) and Pathology (T.A.S.), Duke University Medical Center, Erwin Rd, Durham, NC 27710; and the Department of Radiology, Fundación Dr Enrique Rossi, Buenos Aires, Argentina (S.E.R.). Recipient of a Cum Laude award for a scientific exhibit at the 1999 RSNA meeting. Received January 18, 2000; revision requested March 8 and received May 2; accepted May 12. Address correspondence to J.J.E. (e-mail: erasm001@mc.duke.edu).
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Figure 1a. DAD. (a) Photomicrograph (original magnification, x100; hematoxylin-eosin stain) shows early exudative phase DAD characterized by prominent hyaline membranes (arrows), alveolar septal thickening, and hyperplastic change of type II pneumocytes (arrowheads). (b) Photomicrograph (original magnification, x200; hematoxylin-eosin stain) shows late proliferative phase DAD characterized by interstitial and alveolar duct fibrosis (*) and prominent reactive change in hyperplastic type II pneumocytes (arrows).
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Figure 1b. DAD. (a) Photomicrograph (original magnification, x100; hematoxylin-eosin stain) shows early exudative phase DAD characterized by prominent hyaline membranes (arrows), alveolar septal thickening, and hyperplastic change of type II pneumocytes (arrowheads). (b) Photomicrograph (original magnification, x200; hematoxylin-eosin stain) shows late proliferative phase DAD characterized by interstitial and alveolar duct fibrosis (*) and prominent reactive change in hyperplastic type II pneumocytes (arrows).
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Figure 2. Cyclophosphamide-induced DAD in a 74-year-old woman with breast cancer, progressive dyspnea, and decreased DLCO. Anteroposterior chest radiograph shows bilateral heterogeneous and homogeneous opacities typical for DAD. Diagnosis was confirmed with transbronchial biopsy.
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Figure 3. Daunorubicin-induced DAD in a 43-year-old man with osteosarcoma, fever, dyspnea, and decreased DLCO. High-resolution CT scan shows diffuse thickening of interlobular septa and scattered areas of ground-glass opacity, findings typical of early DAD. No organisms were cultured from transbronchial lavage specimens, and biopsy revealed findings consistent with DAD.
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Figure 4. Bleomycin-induced DAD in a 39-year-old man with a germ cell malignancy, nonproductive cough, and dyspnea. High-resolution CT scan shows scattered areas of ground-glass opacity and thickening of interlobular septa. Architectural distortion and traction bronchiectasis suggest fibrosis due to late-stage DAD. Note right pleural effusion. Transbronchial biopsy revealed findings consistent with late proliferative phase DAD.
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Figure 5. NSIP. Photomicrograph (original magnification, x100; hematoxylin-eosin stain) shows patchy expansion of the interstitium by mononuclear inflammatory cells (arrows), mild interstitial fibrosis (*), and reactive hyperplastic type II pneumocytes (arrowheads).
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Figure 6a. Vincristine and adriamycin-induced NSIP in a 68-year-old woman with myeloma, dyspnea, and fever. (a) Posteroanterior chest radiograph shows bilateral heterogeneous opacities in a lower lung distribution. (b) High-resolution CT scan reveals scattered areas of ground-glass opacity and thickening of interlobular septa. Note minimal architectural distortion. Transbronchial biopsy of the right lower lobe revealed mild, immature fibrosis and mononuclear interstitial infiltrate, findings consistent with NSIP.
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Figure 6b. Vincristine and adriamycin-induced NSIP in a 68-year-old woman with myeloma, dyspnea, and fever. (a) Posteroanterior chest radiograph shows bilateral heterogeneous opacities in a lower lung distribution. (b) High-resolution CT scan reveals scattered areas of ground-glass opacity and thickening of interlobular septa. Note minimal architectural distortion. Transbronchial biopsy of the right lower lobe revealed mild, immature fibrosis and mononuclear interstitial infiltrate, findings consistent with NSIP.
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Figure 7a. Nitrofurantoin-induced NSIP in a 77-year-old woman with chronic urinary tract infection, progressive dyspnea, and cough. (a) Posteroanterior chest radiograph shows bilateral coarse linear opacities in a lower lung distribution. (b) CT scan shows basal areas of conglomerate fibrosis (arrows) and traction bronchiectasis (arrowheads). Transbronchial biopsy showed findings of NSIP, and chest radiography performed 1 month later after discontinuation of nitrofurantoin therapy showed radiologic improvement.
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Figure 7b. Nitrofurantoin-induced NSIP in a 77-year-old woman with chronic urinary tract infection, progressive dyspnea, and cough. (a) Posteroanterior chest radiograph shows bilateral coarse linear opacities in a lower lung distribution. (b) CT scan shows basal areas of conglomerate fibrosis (arrows) and traction bronchiectasis (arrowheads). Transbronchial biopsy showed findings of NSIP, and chest radiography performed 1 month later after discontinuation of nitrofurantoin therapy showed radiologic improvement.
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Figure 8. BOOP. Photomicrograph (original magnification, x40; hematoxylin-eosin stain) shows patchy interstitial inflammation and occlusion of terminal bronchioles and alveolar ducts with plugs of loose edematous connective tissue (arrows).
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Figure 9a. Cyclophosphamide-induced BOOP in a 72-year-old woman with malignant thymoma, fever, nonproductive cough, and dyspnea. (a) Posteroanterior chest radiograph shows scattered, poorly defined peripheral opacities (arrows). (b) Follow-up posteroanterior chest radiograph obtained 2 weeks later shows progressive peripheral consolidation. Wedge resection biopsy of the middle lobe revealed findings of BOOP.
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Figure 9b. Cyclophosphamide-induced BOOP in a 72-year-old woman with malignant thymoma, fever, nonproductive cough, and dyspnea. (a) Posteroanterior chest radiograph shows scattered, poorly defined peripheral opacities (arrows). (b) Follow-up posteroanterior chest radiograph obtained 2 weeks later shows progressive peripheral consolidation. Wedge resection biopsy of the middle lobe revealed findings of BOOP.
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Figure 10. Cyclophosphamide-induced BOOP in a 42-year-old man with nodular sclerosing Hodgkin disease who presented with low-grade fever and decreased DLCO. Chest CT scan shows peripheral, poorly defined areas of focal consolidation and bronchial wall thickening. Note moderate pericardial effusion (P). Transbronchial biopsy showed findings of BOOP.
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Figure 11. Eosinophilic pneumonia. Photomicrograph (original magnification, x200; hematoxylin-eosin stain) shows filling of alveolar space by infiltrate of eosinophils (arrows) and macrophages.
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Figure 12a. Indomethacin-induced eosinophilic pneumonia in a 76-year-old woman with cough and fever. (a) Posteroanterior chest radiograph shows bilateral, peripheral homogeneous opacities. (b) CT scan helps confirm the peripheral distribution of the radiographic findings. Transbronchial biopsy of the right lower lobe showed filling of the alveoli with eosinophils and macrophages, findings consistent with eosinophilic pneumonia.
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Figure 12b. Indomethacin-induced eosinophilic pneumonia in a 76-year-old woman with cough and fever. (a) Posteroanterior chest radiograph shows bilateral, peripheral homogeneous opacities. (b) CT scan helps confirm the peripheral distribution of the radiographic findings. Transbronchial biopsy of the right lower lobe showed filling of the alveoli with eosinophils and macrophages, findings consistent with eosinophilic pneumonia.
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Figure 13. Diffuse alveolar hemorrhage. Photomicrograph (original magnification, x200; hematoxylin-eosin stain) shows acute and organizing intraalveolar hemorrhage (straight arrows), hemosiderin-laden macrophages (curved arrow), and reactive type II pneumocytes (arrowheads).
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Figure 14a. Cytarabine-induced pulmonary hemorrhage in a 30-year-old man with acute leukemia, severe dyspnea, and decreased DLCO. (a) Posteroanterior chest radiograph shows bilateral heterogeneous opacities. (b) High-resolution CT scan shows scattered areas of ground-glass opacity and small bilateral pleural effusions. Transbronchial biopsy of the right upper lobe showed organizing hemorrhage and mild interstitial fibrosis.
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Figure 14b. Cytarabine-induced pulmonary hemorrhage in a 30-year-old man with acute leukemia, severe dyspnea, and decreased DLCO. (a) Posteroanterior chest radiograph shows bilateral heterogeneous opacities. (b) High-resolution CT scan shows scattered areas of ground-glass opacity and small bilateral pleural effusions. Transbronchial biopsy of the right upper lobe showed organizing hemorrhage and mild interstitial fibrosis.
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Figure 15. Acute carmustine pulmonary toxicity in a 23-year-old woman with grade 3 astrocytoma, dyspnea, and decreased DLCO. High-resolution CT scan filmed with narrow window settings (level, -675; window, 650) accentuates the areas of ground-glass opacity present bilaterally. Diagnosis of drug toxicity was presumed because sputum cultures were negative for infection, and the patient's symptoms resolved with cessation of carmustine therapy and administration of corticosteroids.
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Figure 16a. Bleomycin-induced pulmonary toxicity in a 63-year-old man with nonseminomatous germ cell malignancy, nonproductive cough, dyspnea, and decreased DLCO. (a) Chest CT scan demonstrates subtle, subpleural areas of ground-glass and linear opacity (arrows), particularly in the posterior lung bases. (b) Follow-up chest CT scan obtained 3 months later shows increasing subpleural areas of reticular and ground-glass opacity, findings compatible with progressive fibrosis. Diagnosis of drug toxicity was based on clinical findings and the temporal relationship to bleomycin therapy.
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Figure 16b. Bleomycin-induced pulmonary toxicity in a 63-year-old man with nonseminomatous germ cell malignancy, nonproductive cough, dyspnea, and decreased DLCO. (a) Chest CT scan demonstrates subtle, subpleural areas of ground-glass and linear opacity (arrows), particularly in the posterior lung bases. (b) Follow-up chest CT scan obtained 3 months later shows increasing subpleural areas of reticular and ground-glass opacity, findings compatible with progressive fibrosis. Diagnosis of drug toxicity was based on clinical findings and the temporal relationship to bleomycin therapy.
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Figure 17. Bleomycin-induced pulmonary toxicity in a 35-year-old man with nonseminomatous germ cell malignancy, cough, dyspnea, and decreased DLCO. Chest CT scan shows peripheral, poorly defined pulmonary nodules (arrowheads) that were not seen on prior CT scans. Transthoracic needle aspiration biopsy was negative for malignancy, and the nodules resolved after cessation of bleomycin therapy.
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Figure 18a. Amiodarone-induced pulmonary toxicity in a 71-year-old man with a history of refractory ventricular arrhythmia and cough. (a) Posteroanterior chest radiograph shows scattered heterogeneous opacities in the lower lobes and focal homogeneous opacities in the upper lobes (arrows). (b) Non-contrast material-enhanced CT scan reveals high-attenuation consolidation in the right upper lobe, consistent with amiodarone-induced lung injury. (Reprinted, with permission, from reference 26.)
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Figure 18b. Amiodarone-induced pulmonary toxicity in a 71-year-old man with a history of refractory ventricular arrhythmia and cough. (a) Posteroanterior chest radiograph shows scattered heterogeneous opacities in the lower lobes and focal homogeneous opacities in the upper lobes (arrows). (b) Non-contrast material-enhanced CT scan reveals high-attenuation consolidation in the right upper lobe, consistent with amiodarone-induced lung injury. (Reprinted, with permission, from reference 26.)
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Figure 19a. Methotrexate-induced pulmonary toxicity in a 41-year-old woman with rheumatoid arthritis, dyspnea, and decreased DLCO. (a) Posteroanterior chest radiograph shows bilateral heterogeneous opacities in the mid to lower lung zones. (b) High-resolution CT scan shows scattered areas of ground-glass opacity, with thickened interlobular septa—the so-called crazy-paving appearance. Lung biopsy showed NSIP consistent with methotrexate-induced pulmonary toxicity.
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Figure 19b. Methotrexate-induced pulmonary toxicity in a 41-year-old woman with rheumatoid arthritis, dyspnea, and decreased DLCO. (a) Posteroanterior chest radiograph shows bilateral heterogeneous opacities in the mid to lower lung zones. (b) High-resolution CT scan shows scattered areas of ground-glass opacity, with thickened interlobular septa—the so-called crazy-paving appearance. Lung biopsy showed NSIP consistent with methotrexate-induced pulmonary toxicity.
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Figure 20a. Nitrofurantoin-induced pulmonary toxicity in a 63-year-old woman with chronic ureteropelvic junction obstruction and acute respiratory distress. Diagnosis of drug toxicity was based on clinical presentation and exclusion of infection. (a) Posteroanterior chest radiograph shows bilateral heterogeneous opacities. (b) Follow-up posteroanterior chest radiograph obtained 2 months later shows marked improvement in pulmonary opacities after cessation of nitrofurantoin therapy and administration of corticosteroids.
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Figure 20b. Nitrofurantoin-induced pulmonary toxicity in a 63-year-old woman with chronic ureteropelvic junction obstruction and acute respiratory distress. Diagnosis of drug toxicity was based on clinical presentation and exclusion of infection. (a) Posteroanterior chest radiograph shows bilateral heterogeneous opacities. (b) Follow-up posteroanterior chest radiograph obtained 2 months later shows marked improvement in pulmonary opacities after cessation of nitrofurantoin therapy and administration of corticosteroids.
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Figure 21a. Carbotaxol-induced pulmonary toxicity in a 62-year-old man with small cell lung cancer, progressive dyspnea, and fever. (a) Posteroanterior chest radiograph shows new heterogeneous opacities in the left and right upper lobes. (b) High-resolution CT scan shows predominantly left-sided areas of consolidation, thickening of interlobular septa, and traction bronchiectasis. Diagnosis of drug toxicity was based on clinical history, presentation, and exclusion of infection. The patient's symptoms improved following institution of corticosteroid therapy.
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Figure 21b. Carbotaxol-induced pulmonary toxicity in a 62-year-old man with small cell lung cancer, progressive dyspnea, and fever. (a) Posteroanterior chest radiograph shows new heterogeneous opacities in the left and right upper lobes. (b) High-resolution CT scan shows predominantly left-sided areas of consolidation, thickening of interlobular septa, and traction bronchiectasis. Diagnosis of drug toxicity was based on clinical history, presentation, and exclusion of infection. The patient's symptoms improved following institution of corticosteroid therapy.
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Figure 22a. Topotecan-induced pulmonary toxicity in a 45-year-old woman with small cell lung cancer and increasing dyspnea. (a) Posteroanterior chest radiograph shows new heterogeneous opacities in the right lung. Note the mediastinal mass, consistent with small cell lung cancer. (b) Chest CT scan shows areas of ground-glass and linear opacity in the right lung and scattered opacities in the left lung. Wedge resection biopsy of the right upper lobe revealed findings of BOOP.
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Figure 22b. Topotecan-induced pulmonary toxicity in a 45-year-old woman with small cell lung cancer and increasing dyspnea. (a) Posteroanterior chest radiograph shows new heterogeneous opacities in the right lung. Note the mediastinal mass, consistent with small cell lung cancer. (b) Chest CT scan shows areas of ground-glass and linear opacity in the right lung and scattered opacities in the left lung. Wedge resection biopsy of the right upper lobe revealed findings of BOOP.
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Figure 23a. Pulmonary drug toxicity in a 60-year-old woman with non-small cell lung cancer treated with carboplatin and vinorelbine. She presented with progressive dyspnea. (a) CT scan shows a left lower lobe mass (M), mild emphysematous lung disease, and subtle areas of ground-glass opacity in the left lung adjacent to the mass. (b) Follow-up CT scan obtained 5 weeks later shows marked increase in diffuse ground-glass and reticular opacity. Note marked interval improvement in the left lower lobe mass. Diagnosis of drug toxicity was based on clinical history and exclusion of infection. The patient's symptoms and radiologic abnormalities resolved following institution of corticosteroid therapy.
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Figure 23b. Pulmonary drug toxicity in a 60-year-old woman with non-small cell lung cancer treated with carboplatin and vinorelbine. She presented with progressive dyspnea. (a) CT scan shows a left lower lobe mass (M), mild emphysematous lung disease, and subtle areas of ground-glass opacity in the left lung adjacent to the mass. (b) Follow-up CT scan obtained 5 weeks later shows marked increase in diffuse ground-glass and reticular opacity. Note marked interval improvement in the left lower lobe mass. Diagnosis of drug toxicity was based on clinical history and exclusion of infection. The patient's symptoms and radiologic abnormalities resolved following institution of corticosteroid therapy.
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Copyright © 2000 by the Radiological Society of North America.
