Crazy-Paving on CT: Pulmonary alveolar proteinosis and other causes

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1 Chressen Much Gillian Lieberman, MD Crazy-Paving on CT: Pulmonary alveolar proteinosis and other causes Chressen Much University of Tuebingen Harvard Medical School Gillian Lieberman, MD Beth Israel Deaconess Medical Center

2 Definition: Crazy-Paving Crazy-Paving is a pattern seen at thin section CT of the lungs It appears as thickended interlobular septa superimposed on a backround of ground-glass glass attenuation PACS, BIDMC Axial CT of the lungs showing the typical features of Crazy-Paving

3 Index Patient: EA 60 y/o male with Shortness of Breath PACS, BIDMC The radiograph shows extensive airspace opacity in both lungs The axial CT of the lungs shows the characteristic features of Crazy-Paving

4 Differential Diagnosis of Crazy-Paving SANGUINEOUS SANGUINEOUS Acute Acute Respiratory Respiratory Distress Distress Syndrome Syndrome Pulmonary Pulmonary Hemorrhage Hemorrhage Syndromes Syndromes INFECTION INFECTION Pneumocystis Pneumocystis Pneumonia Pneumonia Causes INHALATION INHALATION Lipoid Lipoid Pneumonia Pneumonia NEOPLASM NEOPLASM Bronchioloalveolar Bronchioloalveolar Carcinoma Carcinoma IDIOPATHIC IDIOPATHIC Pulmonary Pulmonary alveolar alveolar proteinosis proteinosis Nonspecific Nonspecific Interstitial Interstitial Pneumonia Pneumonia Organizing Organizing Pneumonia Pneumonia

5 Additional notes about Crazy-Paving 1. Crazy-Paving was originally described in patients with Pulmonary alveolar proteinosis and is very characteristic for this disease 2. But Crazy-Paving is really a very nonspecific finding and can been seen in a variety of diffuse lung diseases 3. Note that most diseases on the differential list don t necessarily present with Crazy-Paving

6 Pneumocystis Pneumonia Common pulmonary infection in severely immunocompromised patients CD4-cell counts < 200 cells/??? Infection Patient presents with acute onset of fever, cough and progressive dyspnea Typically bilateral, perihilar ground-glass opacities due to foamy nature of the alveolar exudates Interlobular septal thickening due to edema and cellular infiltrates Typical pneumocystis cyst forms in a bronchoalveolar lavage specimen stained with Gomori methenamine PACS, BIDMC Coronal CT of the lungs showing ground glass opacities and septal thickening in a perihilar distribution Thomas, CF, Limper, AH. Pneumocystis Pneumonia. N Engl J Med :2487.;

7 Bronchioloalveolar carcinoma Rossi, S. E. et al. Radiographics 2003;23: Axial CT of the lungs showing bilateral BAC Neoplasm Patients present with cough, shortness of breath, hemoptysis, weight loss, and fever Lepidic growth pattern (along intact alveolar septa) with preservation of the underlying lung architecture Rossi, S. E. et al. Radiographics 2003;23: Mucinous tumor cells infiltrate the alveolar wall Ground-glass attenuation reflects the intra-alveolar glycoprotein secreted by the tumor cells; septal thickening is due to infiltration with tumor cells and inflammatory cells Multicentric development of lesions due to aerogenous and lymphatic spread

8 Lipoid Pneumonia Inhalation Chest radiograph showing an infiltrate in the right middle lobe. -85 HU Rossi, S. E. et al. Radiographics 2003;23: Axial CT of the lungs showing a consolidation with fat attenuation in the right lower lobe Gaerte, S. C. et al. Radiographics 2002;22:S61-S78 Results from chronic aspiration of (mineral, vegetable, animal) oils into the lungs Predisposing factors: neuromuscular disorders, structural disorders of the pharynx, esophageal disorders, chronic illness Most common location are the dependent portions of the lungs Most characteristic finding on CT is lung consolidation with fat attenuation

9 Acute respiratory distress syndrome Two axial CTs of the lungs showing Crazy-Paving in patients with ARDS Sanguineous Rossi, S. E. et al. Radiographics 2003;23: Gluecker, T. et al. Radiographics 1999;19: ARDS is a form of pulmonary edema Acute and persistent lung inflammation with increased vascular permeability Causes/predisposing factors: Shock, sepsis, aspiration, infection, trauma, drug/alcohol abuse etc. Bilateral infiltrates ground-glass opacities and septal thickening represent edema of the alveoli and the perivascular spaces and filling of the alveoli with protein-rich fluid

10 Pulmonary Hemorrhage Syndromes Sanguineous Rossi, S. E. et al. Radiographics 2003;23: Axial CT of the lungs showing ground-glass opacities and septal thickening in a patient with diffuse alveolar hemorrhage JK Thomas, K Jayaprakash, KJR Misiriya, SA Khadar, JM Pappachan; Chest Radiograph showing diffuse alveolar infiltrates Patients present with hemoptysis, dyspnea, fever and anemia Onset of symptoms is most often acute or of short duration Important causes are: systemic vasculitides (Wegener s granulomatosis), connective tissue disease (SLE, Goodpasture s syndrome) drugs (anticoagulant therapy, amiodarone, crack cocaine), infection (opportunistic infections, viral), etc.

11 More Causes of diffuse Alveolar Hemorrhage Syndromes Causes of diffuse alveolar hemorrhage syndromes (DAH) based on histologic appearance Capillaritis Systemic vasculitides Beh et's syndrome Cryoglobulinemia Henoch-Schoenlein purpura IgA nephropathy Pauci-immune glomerulonephritis Wegener's granulomatosis Connective tissue disease Mixed connective tissue disease Goodpasture's syndrome* Polymyositis Primary antiphospholipid antibody syndrome Rheumatoid arthritis Systemic lupus erythematosis* Systemic sclerosis Drugs Diphenylhydantoin Propylthiouracil Retinoic acid syndrome Other Autologous hematopoietic cell transplantation Idiopathic pulmonary hemosiderosis Infective endocarditis Isolated pulmonary capillaritis Leptospirosis Lung transplant rejection Bland Hemorrhage Connective tissue disease Goodpasture's syndrome* Systemic lupus erythematosis* Drugs Anticoagulant therapy Platelet glycoprotein IIA/IIIB Other Idiopathic pulmonary hemosiderosis Leptopirosis Mitral stenosis Pulmonary veno-occlusive disease Diffuse alveolar damage Infection Any infection causing ARDS Opportunistic infections in immunocompromised host Viral Connective tissue disease Polymyositis Systemic lupus erythematosis Drugs Amiodarone Crack cocaine Cytotoxic drugs Nitrofurantoin Penicillamine Propylthiouracil Sirolimus Other Acute respiratory distress syndrome (any cause) Pulmonary capillary hemangiomatosis Pulmonary infarction Trimellitic anhydride Tuberous sclerosis

12 Continued patient workup PACS, BIDMC year-old male with history of ILD who presented with acute shortness of breath for several days that rapidly progressed to hypoxic respiratory failure 2. No improvement despite being on steroids for several weeks 3. Tobacco: 50 pack-years 4. No recent changes in weight. No fatigue, fever, chills or night sweats

13 Pulmonary Alveolar Proteinosis Idiopathic Accumulation of PAS-positive lipoproteinaceous material in the distal air spaces Impaired processing of surfactant by alveolar macrophages Patients present with dyspnea and nonproductive cough Interlobular thickening is due to type II epithelial cell hyperplasia PACS, BIDMC Coronal CT of the lungs (patient EA) showing extensive bilateral Crazy-Paving Radiologic findings: Diffuse bilateral ground-glass opacity, with superimposed intra/ and interlobular septal thickening (Crazy-Paving)

14 Making the Diagnosis of Pulmonary Alveolar Proteinosis

15 Making the Diagnosis of Pulmonary Alveolar Proteinosis Bronchoalveolar lavage: Transbronchial biopsy PAS-positive lipoproteinacious material in the lavage specimen thick layer of dense proteinaceous material at the bottom The alveoli are filled with a flocculent and granular lipoproteinaceous material that stains pink with PAS stain From Keller, CA, Frost, A, Cagle, PT, Abraham, JL, Chest 1995; 108:277. Talmadge E King, Jr, MD A biopsy was taken in patient EA and it proved to be PAP

16 Therapy of Pulmonary Alveolar Proteinosis The most widely accepted and effective form of treatment is a therapeutic whole lung lavage via a double-lumen endotracheal tube. Axial lung CT pre-lavage showing extensive ground-glass opacity and septal thickening PACS, BIDMC Axial lung CT post-lavage showing dramatic improvement in ground-glass opacities and septal thickening A therapeutic lung lavage was performed in patient EA The post-lavage lung CT shows marked improvement in the diffuse ground-glass opacity and intervening interlobular septal thickening

17 Prognosis of Pulmonary alveolar proteinosis Some patients are asymptomatic with little or no physiologic impairment despite extensive radiographic abnormalities Approximately 25% of patients experience spontaneous remission 30 to 40 percent of patients require only one lavage Most patients will require repeat lung lavages at intervals of 6-12 months

18 Questions that may guide you to the right diagnosis: Is the condition acute or chronic? Is the patient immunocompromised? Is the patient ventilated? Does the patient have an underlying condition that puts him at risk for diffuse alveolar bleeding? Does the patient present with any symtoms that make you think about neoplasm?

19 Summary 1. Crazy-Paving appearance consists of interlobular septal thickening superimposed on an area of ground-glass opacity on CT of the lungs 2. Crazy-Paving is characteristic for PAP, yet many other diseases can show this appearance on CT; Crazy-paving is a nonspecific finding 3. The various disease entities that cause crazy paving can often be distinguished by their clinical findings and patient history

20 References: Rosen, et al. Pulmonary alveolar proteinosis. N Engl J Med 1958; 258:1123 Trapnell, et al. Pulmonary alveolar proteinosis. N Engl J Med 2003;349: Alberti, et al. Bronchoalveolar lavage fluid composition in alveolar proteinosis. Early changes after therapeutic lavage. Am J Respir Crit Care Med 1996;154:817 Goldstein, et al. Pulmonary alveolar proteinosis. Clinical features and outcomes. Chest 1998; 92:2657 Holbert, et al. CT features of pulmonarzy alveolar proteinosis. AJR Am J Roentgenol 2001; 176:1287 Johkoh, et al. Crazy-paving appearance at thin-section CT: Spectrum of disease and pathologic findings. Radiology 1999; 211:155 Santiago, et al. Crazy-paving Pattern at Thin-Section CT of the Lungs: Radiologic-Pathologic Overviev. RadioGraphics 2003;23: Gruden, et al. High-Resolution CT in the evaluation of clinically suspected Pneumocystis carinii pneumonia in AIDS patients with normal, equivocal, or nonspecific radiographic findings. AJR Am J Roentgenol 1997;169:967 Kovacs, et al. New insights into transmission, diagnosis, and drug treatment of Pneumocystis carinii pneumonia. JAMA 2001; 286:2450 Lee, et al. Bronchioloalveolar carcinoma: clinical, histopathologic, and radiologic findings. Radio-Graphics 1997;17: Gaerte, et al. Fat-containing Lesions of the Chest. Radio-Graphics 2002; 22: S61-S78 Gluecker, et al.clinical and Radiologic Features of Pulmonary Edema. RadioGraphics 1999; 19: Collard, et al. Diffuse alveolar hemorrhage. Clin Chest Med 2004;25:583 Bradley, JD. The pulmonarz hemorrhage syndromes. Clin Chest Med 1982;3:

21 Acknowledgments Paul W. Spirn, MD Michael G. Geary, MD Gillian Lieberman, MD Maria Levantakis

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