Residents Section Pattern of the Month

Residents Section Pattern of the Month Gosset et al. Tree-In-Bud Pattern Residents Section Pattern of the Month Residents inradiology Natacha Gosset 1 Alexander A. Bankier Ronald L. Eisenberg Gosset N, Bankier AA, Eisenberg RL Keywords: bronchial disorders, CT, lung DOI:10.2214/AJR.09.3401 Received July 28, 2009; accepted after revision August 18, 2009. 1 All authors: Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave., Boston, MA 02215. Address correspondence to R. L. Eisenberg (rleisenb@bidmc.harvard.edu). WEB This is a Web exclusive article. Tree-In-Bud Pattern Tree-in-bud (Fig. 1) refers to a pattern seen on thin-section chest CT in which centrilobular bronchial dilatation and filling by mucus, pus, or fluid resembles a budding tree (Fig. 2). Usually somewhat nodular in appearance, the tree-in-bud pattern is generally most pronounced in the lung periphery and associated with abnormalities of the larger airways. Normal lobular bronchioles ( 1 mm in diameter) cannot be seen on CT scans, which can only show bronchi more than 2 mm in diameter. However, diseased bronchioles can be seen. Therefore, the tree-in-bud pattern is indicative of a spectrum of endo- and peribronchiolar disorders with dilatation; bronchiolar wall thickening; peribronchiolar inflammation; and bronchiolar luminal impaction with mucus, pus, fluid, or, as described more recently, tumor emboli. First described in cases of endobronchial spread of Mycobacterium tuberculosis, the tree-in-bud pattern is now recognized as a CT manifestation of such various entities as infection (bacterial, fungal, TABLE 1: Causes of Tree-In-Bud Pattern Infections Bacterial Fungal Viral Congenital disorders Cystic fibrosis Kartagener syndrome Idiopathic disorders Obliterative bronchiolitis Diffuse panbronchiolitis Aspiration or inhalation of foreign substances Immunologic disorders Allergic bronchopulmonary aspergillosis Connective tissue disorders Rheumatoid arthritis Sjögren syndrome Peripheral pulmonary vascular disease AJR 2009; 193:W472 W477 0361 803X/09/1936 W472 American Roentgen Ray Society Fig. 1 Tree-in-bud sign seen in photograph of magnolia tree just outside of our hospital shows typical combination of branching (white arrows) and buds (black arrows). Fig. 2 Image shows classic CT appearance of treein-bud opacities, consisting of branching structures (black arrows) and buds (white arrows). W472 AJR:193, December 2009

Tree-In-Bud Pattern viral, parasitic), congenital disorders (cystic fibrosis, Kartagener syndrome), idiopathic disorders (obliterative bronchiolitis, panbronchiolitis), aspiration or inhalation of foreign substances, immunologic abnormalities, connective tissue disorders, and peripheral pulmonary vascular disease (neoplastic pulmonary emboli) (Table 1). Additional imaging findings combined with history and clinical presentation can suggest the appropriate diagnosis. Infections Bacterial Infection The classic cause of the tree-in-bud pattern is postprimary tuberculosis (Fig. 3), a condition that develops in approximately 5% of patients with primary infection and is frequently associated with malnutrition and immune suppression. Occasionally, it may reflect reinfection with new organisms. The tree-in-bud pattern suggests active and contagious disease, especially when associated with adjacent cavitary disease within the lungs. The most common CT findings are centrilobular nodules and branching linear and nodular opacities. This tree-in-bud pattern is due to the presence of caseation necrosis and granulomatous inflammation within and surrounding the terminal and respiratory bronchioles and alveolar ducts, reflecting endobronchial spread of tuberculosis. Other common findings include cavitary nodules, lobular consolidation, interlobular thickening, and bronchovascular distortion. Pleural effusion and enlarged lymph nodes with central low attenuation due to caseous necrosis also can be seen. After antituberculous therapy is begun, most of the centrilobular and branching opacities disappear within 5 months. However, bronchovascular distortion, fibrosis, emphysema, and bronchiectasis increase on follow-up CT. Atypical mycobacteria may produce a pattern indistinguishable from that of tuberculosis, although without any upper lobe predominance (Fig. 4). This is also seen with Mycobacterium avium-intracellulare or M. avium complex, notably in immunologically compromised individuals with HIV. Bronchiolitis due to Staphylococcus aureus and Haemophilus influenzae also may manifest as the peripheral tree-in-bud pattern. Fungal Infection Invasive airway aspergillosis causing bronchiolitis occurs most commonly in neutropenic patients and individuals who are immunologically suppressed with AIDS. Fungal hyphae are often found in the airway lumen. Other clinical manifestations of this condition are bronchopneumonia (peribronchial distribution of consolidation) and tracheobronchitis (bronchiectasis A Fig. 3 Tuberculosis. A and B, Peripheral tree-in-bud opacities (circle, A) combine to produce more peripheral centrilobular nodules (circle, B). B AJR:193, December 2009 W473

Gosset et al. A Fig. 4 Atypical mycobacterial infection. A and B, Maximum-intensity-projection images in transverse (A) and coronal (B) planes show generalized treein-bud opacities. and thickening of the trachea or bronchi), which are often bilateral. Invasive airway aspergillosis should be suggested when the tree-in-bud pattern occurs in combination with a consolidation accompanied by a halo of ground-glass opacity in a patient with leukemia. Viral Infection Cytomegalovirus infection, which typically occurs in immunologically compromised individuals, can cause bronchiolitis with centrilobular nodules and thickening of the bronchovascular bundles that produce the tree-in-bud pattern. This pattern may have a patchy and unilateral or bilateral and asymmetric distribution and may progress to areas of ground-glass opacity and consolidation. There may be poorly defined nodules with the CT halo sign. In infants and young children, the tree-in-bud pattern is most commonly caused by bronchial wall thickening and dilatation related to respiratory syncytial virus. Congenital Disorders Cystic Fibrosis Cystic fibrosis is an autosomal-recessive hereditary disorder involving the exocrine glands, resulting in the production of abnormal secretions by the salivary and sweat glands, pancreas, large bowel, deferent ducts, and tracheobronchial tree. A block in the transport of chloride into the bronchial lumen and the excessive resorption of sodium leads to the production of thick and dry mucus, resulting in decreased clearance of mucus and eventually mucous plugging in small and large airways and subsequent bacterial infection. Chronic infection and inflammatory reactions cause lung damage. The most common CT findings include bronchial wall thickening, bronchiectasis or bronchiolectasis, mucous plugging, and air trapping on expiratory scanning. Large amounts of bronchiolar secretions can produce the tree-in-bud pattern, which predominantly tends to affect the upper lobes in the early stage of the disease. Kartagener Syndrome Kartagener syndrome is one of the dyskinetic cilia syndromes, a set of autosomal-recessive disorders in which inherited abnormalities in ciliary structure and function result in abnormal mucociliary clearance and chronic infection. It is characterized by the clinical triad of situs inversus, sinusitis, and bronchiectasis. Symptoms of recurrent bronchitis, pneumonia, and sinusitis often date from childhood. In men, the syndrome may be associated with immotile spermatozoa and infertility. The typical chest CT findings in Kartagener syndrome include bilateral bronchiectasis with a basal predominance. Airway damage can extend to the smaller airways, causing bronchiolectasis, air trapping, and centrilobular opacities producing the tree-in-bud pattern. B W474 AJR:193, December 2009

Tree-In-Bud Pattern Idiopathic Disorders Obliterative Bronchiolitis Obliterative bronchiolitis, also known as constrictive bronchiolitis, is an irreversible fibrosis of small airway walls that narrows or obliterates the lumen, leading to chronic airway obstruction. The most common causes include infection (viral, bacterial, mycoplasma), inhalation of toxic fumes, drug treatment (penicillamine or gold), collagen vascular disease (rheumatoid arthritis, especially after the therapies mentioned), chronic lung transplant rejection, and bone marrow transplantation with chronic graft-versus-host disease. Nevertheless, obliterative bronchiolitis is often idiopathic. Patients usually present with shortness of breath and evidence of airway obstruction. CT findings include bronchial wall thickening, central and peripheral bronchiectasis, mosaic perfusion, and air trapping on expiratory CT scans (the most sensitive sign). Centrilobular nodules from luminal impaction produce the tree-in-bud pattern (Fig. 5). Fig. 5 Obliterative bronchiolitis. CT image shows extensive right lower lobe area of peripheral treein-bud opacities (arrows). Nodular component of opacities is smaller but well defined. Diffuse Panbronchiolitis Diffuse panbronchiolitis is a progressive inflammatory disease of unknown cause that has been reported almost exclusively in Japan and Eastern Asia. It represents a transmural infiltration of lymphocytes and plasma cells, with mucus and neutrophils filling the lumen of affected bronchioles. Most affected individuals are nonsmokers and have chronic sinusitis. The natural history of the disease is progressive respiratory failure leading to cor pulmonale and ultimately death. In addition to thick-walled bronchioles filled with mucus and producing the tree-in-bud pattern, there may be nodules, bronchiectasis, large cystic opacities accompanied by dilated proximal bronchi, and mosaic perfusion or air trapping. Aspiration or Inhalation of Foreign Substances Aspiration of infected oral secretions or other irritant material into the bronchioles can lead to a chronic inflammatory reaction. Predisposing factors include structural abnormalities of the pharynx, esophageal disorders (achalasia, Zenker diverticulum, hiatal hernia and reflux, esophageal carcinoma), neurologic defects, and chronic illness. In acute cases, extensive exudative bronchiolar disease may develop and result in centrilobular nodules and the tree-in-bud pattern in a distribution characteristic of aspirated material. Inhalation of toxic fumes and gases can cause pulmonary damage. Acutely, it leads to alveolocapillary damage with subsequent pulmonary edema, bronchitis, and bronchiolitis and AJR:193, December 2009 W475

Gosset et al. Fig. 6 Chronic aspiration. Tree-in-bud opacities (arrows) in right lower lobe. Note hiatal hernia. Nodular component of changes may later coalesce and create ground-glass appearance. may be complicated by atelectasis and pneumonia. Chronically, it can result in obliterative bronchiolitis. CT findings include bronchial wall thickening, bilateral consolidation, bronchiectasis, and the tree-in-bud pattern (Fig. 6). Immunologic Disorders Allergic bronchopulmonary aspergillosis is a hyperimmune response to airway colonization with Aspergillus species commonly seen in patients with asthma and cystic fibrosis. The fungus proliferates in the proximal bronchi, acting as an antigenic stimulus for the production of IgE and IgG antibodies. The inflammatory reaction results in damage to the bronchial wall, central bronchiectasis, and the formation of mucous plugs that contain fungus and inflammatory cells, producing the finger-in-glove sign of large airway impaction that tends to have upper lobe predominance and can be seen on chest radiographs. Involvement of the small airways causes the tree-in-bud pattern (Fig. 7). Indirect signs of small airways disease include a mosaic pattern of lung attenuation and air trapping on expiratory scanning. A Fig. 7 Allergic bronchopulmonary aspergillosis. A and B, Peripheral tree-in-bud opacities (arrows, A) can often be accompanied by more proximal airway abnormalities, such as mucous plugging (arrows, B). Connective Tissue Disorders Rheumatoid Arthritis Rheumatoid arthritis is twice as common in women, although extraarticular manifestations (including lung disease) are more common in men. About 90% of patients have a positive serum rheumatoid factor and show clinical evidence of arthritis before developing pulmonary or pleural disease. The most common thoracic abnormalities include interstitial pneumonia and fibrosis, pleural effusion or pleural thickening, necrobiotic nodules, organizing pneumonia, bronchiectasis, and obliterative bronchiolitis. B W476 AJR:193, December 2009

Tree-In-Bud Pattern Fig. 8 Rheumatoid arthritis. Axial CT image shows tree-in-bud opacities (arrows) in lingula. A lymphoid interstitial infiltrate in the walls of the small airways (follicular bronchiolitis) may cause small centrilobular nodules and the tree-in-bud pattern (Fig. 8). More extensive lymphocytic infiltrations may be associated with lymphoid interstitial pneumonia (LIP), with groundglass opacities, consolidation, septal thickening mimicking the lymphangitic spread of carcinoma, and cystic air spaces. This condition progresses to fibrosis in about one third of patients. Sjögren Syndrome Sjögren syndrome consists of the clinical triad of keratoconjunctivitis sicca, xerostomia, and recurrent swelling of the parotid gland. The most common thoracic manifestations include LIP (more common than in rheumatoid arthritis), follicular bronchiolitis, interstitial pneumonia, organized pneumonia, tracheobronchial gland inflammation, and pleuritis with or without effusion. As with rheumatoid arthritis, lymphoid interstitial infiltrate in the walls of the small airways may produce the tree-in-bud pattern. Peripheral Pulmonary Vascular Disease The lung is a frequent site of tumor embolism, most commonly from choriocarcinoma and primary malignancies of the liver, breast, kidney, stomach, and prostate. Filling of the centrilobular arteries with tumor cells or a rare widespread fibrocellular intimal hyperplasia of small pulmonary arteries (carcinomatous endarteritis) may produce the tree-in-bud pattern. Affected patients present with progressive dyspnea and cough and signs of hypoxia and pulmonary hypertension (due to increased pulmonary vascular resistance). Suggested Reading 1. Collins J, Blankenbaker D, Stern EJ. CT patterns of bronchiolar disease: what is tree-in-bud? AJR 1998; 171:365 370 2. Eisenhuber E. The tree-in-bud sign. Radiology 2002; 222:771 772 3. Hansell DM. Small airways diseases: detection and insights with computed tomography. Eur Respir J 2001; 17:1294 1313 4. Bankier AA, Van Muylem A, Knoop C, et al. Bronchiolitis obliterans syndrome in heart lung transplant recipients: diagnosis with expiratory CT. Radiology 2001; 218:533 539 5. Franquet T, Giménez A, Prats R, Rodríguez-Arias JM, Rodríguez C. Thrombotic microangiopathy of pulmonary tumors: a vascular cause of tree-in-bud pattern on CT. AJR 2002; 179:897 899 6. Hansell DM, Bankier AA, MacMahon H, McLoud TC, Müller NL, Remy J. Fleischner Society: glossary of terms for thoracic imaging. Radiology 2008; 246:697 722 7. Müller NL, Silva CIS. Imaging of the chest: expert radiology series. New York, NY: Saunders, 2008 8. Rossi SE, Franquet T, Volpacchio M, et al. Tree-in-bud pattern at thin-section CT of the lungs: radiologic pathologic overview. RadioGraphics 2005; 25:789 801 9. Webb WR, Higgins CB. Thoracic imaging: pulmonary and cardiovascular radiology. Philadelphia, PA: Lippincott Williams & Wilkins, 2005 AJR:193, December 2009 W477