Micronodular lung pattern - Differential diagnosis

Transcription

1 Micronodular lung pattern - Differential diagnosis Poster No.: P-0074 Congress: ESTI 2015 Type: Educational Poster Authors: P. Ninitas, F. Marinho, P. Campos, I. Távora ; Lisbon/PT, Funchal/PT, Cascais/PT Keywords: Education and training, Education, Diagnostic procedure, CT-High Resolution, CT, Lung DOI: /esti2015/P-0074 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 22

2 Learning objectives To recognize the micronodular lung pattern in a high-resolution CT (HRCT). To identify the predominant distribution of the micronodules: centrilobular, perilymphatic or random. To make a differential diagnosis based on the location of the micronodules. Know the diseases that may cause the diffuse micronodular lung disease and their predominant features. Background A pulmonary micronodule is a discrete, small, round, focal opacity with less than 3mm in diameter (1). The micronodular lung pattern consists of multiple pulmonary micronodules (1,2,3). The distribution is widespread but not necessarily uniform (1). On CT scans, the micronodular pattern may be classified based on their anatomic distribution: centrilobular, lymphatic, or random (1). For this purpose it is essential to understand the secondary lobular anatomy of the lung. The secondary pulmonary lobule is defined as the smallest unit of lung function marginated by connective tissue septa - the interlobular septa (1,2,3). The core or centrilobular structures include bronchioles, their accompanying pulmonary arterioles and lymphatic vessels (1,2). Within the secondary pulmonary lobule is the intralobular interstitium, a series of connective tissue fibers that suspend the various lobular structures (2). Investing the bronchi and pulmonary arteries it is the peribronchovascular interstitium that surrounds these structures in the perihilar lung - axial fiber system (3). The more peripheral continuum of this interstitial fiber system surrounds small centrilobular bronchioles and arteries (3). Pulmonary veins and lymphatics course in the periphery of the lobule within the interlobular septa (2). The peripheral interstitium extends over the surface of the lung beneath the visceral pleura and envelopes the lung in a fibrous sac from which the connective tissue septa penetrate the lung parenchyma (3). Secondary pulmonary lobules in the lung periphery are relatively large and are marginated by interlobular septa that are thicker and better defined than lobules in other parts of the lung, whereas the secondary lobules in the central lung zone are smaller and more irregular in shape (3). Page 2 of 22

3 Centrilobular micronodules are distributed primarily within the center of the secondary pulmonary lobule (2). They usually are positioned about 5 to 10 mm from the visceral pleural surface (2,4). When these micronodules are present it means that the structures in the center of the pulmonary lobule are affected: bronchiole, artery or the interstitium peribronchiolar or periarterial (2,4). Perilymphatic micronodules are found along the pulmonary lymphatics: in the interlobular septa, in the visceral pleura and within the center of the secondary lobule (2). Interlobular and subpleural micronodules are present in great number with very few centrilobular micronodules (2,4). Random micronodules are seen in the center of the lobule and in contact with interlobular septa and visceral pleural surfaces, like the perilymphatic ones (2). However, the distribution of the random micronodules is diffuse without a predominant topography (2). Images for this section: Page 3 of 22

4 Fig. 1: Secondary Pulmonary Lobule Page 4 of 22

5 Fig. 2: Centrilobular disease Page 5 of 22

6 Fig. 3: Perilymphatic disease Page 6 of 22

7 Fig. 4: Random distribution of the micronodules Page 7 of 22

8 Imaging findings OR Procedure details High-resolution computed tomography (HRCT) provides a more accurate vision of the lung parenchyma than chest radiographs in the presence of diffuse lung disease (5). HRCT reveals features that can clarify the diagnosis when chest radiograms are inconclusive due to its ability to evaluate the lung parenchyma in cross-section, eliminating the superimposition of densities (4,5). On thin-section CT scans, the three basic components of the lobule - the interlobular septa and septal structures, the central lobular region (centrilobular structures), and the lobular parenchyma-can be identified (1). Localizing nodules on HRCT begins first with assessing the nodules in contact with the visceral pleura surfaces or fissures (subpleural nodules). If there is a significant proportion of subpleural nodules it could be a perilymphatic or random distribution: the distinction is that the perilymphatic nodules are predominantly found along interlobular septa and visceral pleura (centrilobular nodules are scarce) and the random nodules are even distributed along the central components and the periphery of the secondary lobule without preference (2,4,5). On the other hand if there are absence or only a very few subpleural nodules it is a centrilobular distribution (2,4). Once one identifies a perilymphatic distribution it indicates that there is a disease involving preferentially the lymphatic structures. In this category, the main diseases to be considered are sarcoidosis and lymphangitic carcinomatosa. Other diagnoses for this pattern of disease are silicosis, coal worker pneumoconiosis, lymphocytic interstitial pneumonia, lymphoproliferative disorders and amyloidosis (2,4). In sarcoidosis the micronodules are found most often in the subpleural and peribronchovascular interstitium and less often in the interlobular septa. They usually have a bilateral and symmetric distribution, predominantly but not invariably in the upper and middle zones and are sharply defined (6,7). The most common tumors that spread within the pulmonary lymphatics (lymphangitic carcinomatosa) are carcinomas of the bronchus, breast, pancreas, stomach, colon, and prostate. CT shows a non-uniform, nodular, thickening of the interlobular septa and the bronchovascular bundles, often with patchy airspace opacities. The distribution of the Page 8 of 22

9 changes varies greatly: may involve all zones of both lungs or they may be centrally or peripherally predominant; sometimes they are confined to a lobe or one lung (8,9). Random micronodules don't have a definable distribution relative to the secondary pulmonary lobule: they are seen in the center of the lobule and in contact with interlobular septa and visceral pleural surfaces. Random micronodules, in contrast to perilymphatic ones, do not show a patchy distribution in the lung parenchyma and they are usually spread uniformly throughout the lung parenchyma in a bilaterally symmetric distribution (2). The differential diagnosis includes hematogenous metastases, infections (fungal, viral, tuberculosis) and less frequently, silicosis, coal-worker's pneumoconiosis, Langerhans cell histiocytosis, septic emboli and pulmonary vasculitides (2,5). Hematogenous metastases are frequently due to metastatic thyroid cancer, renal cancer, and melanoma; while larger less profuse metastases tend to be adenocarcinomas in adults, typically originating from the lung, breast, or the GI tract (4). Hematogenous metastases typically have a peripheral and basal predominance when limited in number but a uniform distribution when there are innumerable lesions and are relatively uniform in size (5,6). Hematogenous dissemination of tuberculosis, also called miliary tuberculosis, shows multiple micronodules with a random pattern. Ground-glass areas with a variable extension and patchy appearance could be present (5,6). Differentiation between infection and tumor may be impossible to determine by imaging features alone, in general, the clinical history renders these diagnoses relatively straightforward (4,5,6). The micronodules in silicosis have an upper and posterior predominance in mild disease. Centrilobular and subpleural micronodules are common. The complicated disease originates progressive massive fibrosis (6). Centrilobular micronodules can reflect the presence of either interstitial or airspace abnormalities, so they are most commonly seen in patients with disease that primarily affects centrilobular bronchioles and results in inflammation, infiltration or fibrosis of the surrounding interstitium and alveoli (3). On thin-section CT scans, they usually appear to be separated from the pleural surfaces, fissures, and interlobular septa by a distance of at least several millimeters, therefore they are seen to be related to centrilobular structures, even if they cannot be precisely localized to the centers of secondary lobules. Centrilobular micronodules may be dense and of homogeneous attenuation or of groundglass opacity (3). Page 9 of 22

10 Once nodules are identified as centrilobular, one should search for tree-in-bud - small centrilobular nodules of soft-tissue attenuation connected to multiple branching linear structures of similar caliber originating from a single stalk that end several millimeters distant from nearby pleural or fissural surfaces (3,4,5,10). The tree-in-bud sign usually reflects the presence of dilated centrilobular bronchioles with lumina that are impacted with mucus, fluid, or pus; it is often associated with peribronchiolar inflammation (3). The tree-in-bud sign is usually associated with other abnormal findings visible on thin-section CT scans: bronchiolar (dilatation and wall thickening are sometimes seen) and large-airways abnormalities (bronchial wall thickening or bronchiectasis) (3). Another frequently encountered finding in patients with bronchiolar disease is mosaic attenuation (4,10). Centrilobular micronodules with tree-in-bud sign is seen in infectious bronchiolitis (bacterial, viral, fungal, typical and atypical mycobacterial infections), allergic bronchopulmonary aspergillosis, cystic fibrosis, diffuse panbronchiolitis and endobronchial neoplasms (particularly adenocarcinoma in situ) (2,4,10). In patients with endobronchial spread of tuberculosis the presence of centrilobular micronodules and tree-in-bud is highly suggestive of active disease. Associated highresolution CT findings include bronchial wall thickening with or without bronchiectasis. Consolidation, cavitation, pleural effusion, and lymphadenopathy with central necrosis can also be seen (10). Infection with pulmonary nontuberculous mycobacteria has radiologic manifestations similar to those in patients with post primary tuberculosis in its classic form (10). Airway-invasive aspergillosis is a mycotic disease caused by Aspergillus species, usually A fumigatus. It is most commonly seen in immunocompromised neutropenic patients and patients with acquired immunodeficiency syndrome (AIDS). Bronchiolitis is characterized at thin-section CT by the presence of centrilobular nodules and linear branching opacities producing a tree-in-bud appearance (10). When centrilobular nodules are present but tree-in-bud morphology is absent, it indicates a disease that affect the centrilobular portion of the secondary lobule: the centrilobular bronchiole, peribronchiolar or perivascular (4). This includes diseases that primarily affect the centrilobular bronchiole, as well as those primarily peribronchiolar or perivascular in origin (4). The peribronchiolar distribution results in a pattern of diffuse, poorly defined ground-glass nodules and the differential Page 10 of 22

11 diagnosis encompasses several diseases: hypersensitivity pneumonitis, respiratory bronchiolitis (RB), Langerhans cell histiocytosis (LCH) and pneumoconiosis (especially silicosis and coal-worker's pneumoconiosis). Diseases related to bronchiolar lymphatics are also included in the differential diagnosis: lymphocytic interstitial pneumonitis (LIP) and mucosa-associated lymphoid tissue lymphoma (maltomas). The perivascular origin includes vasculitis, pulmonary edema and pulmonary hypertension (2,4,5). On thin-section CT, hypersensitivity pneumonitis appears acutely as small, ill-defined centrilobular nodules and bilateral airspace consolidation. In the subacute stage, there are patchy ground-glass opacities with ill-defined centrilobular nodules. Mosaic perfusion generally affects the middle and lower lung (4,5). RB typically produces faint micronodular nodules and patchy ground-glass opacities predominantly involving the upper lobes. Moderate centrilobular emphysema is common, given that most patients have a smoking history (5,10). Lymphocytic interstitial pneumonitis (LIP) is usually secondary to systemic diseases: Sjogren syndrome, human immunodeficiency virus infection, and variable immunodeficiency syndromes (10). Occasionally centrilobular nodules, septal thickening and ground-glass attenuation are identified, but most frequently thin-walled perivascular cysts are seen. Bilateral abnormalities are diffuse or have lower lung predominance (10). Images for this section: Page 11 of 22

12 Fig. 5: Diagnostic Algorithm - micronodular disease. Adapted from 2,4 and 11 Fig. 6: Diferential diagnosis of the perilymphatic diseases Page 12 of 22

13 Fig. 7: Sarcoidosis. Perilymphatic distribution of micronodules - along the fissures and peribronchovascular interstitium. Page 13 of 22

14 Fig. 8: Sarcoidosis. Perilymphatic distribution of micronodules - perihilar interstitial micronodules Page 14 of 22

15 Fig. 9: Lymphangitic Carcinomatosa. Thickening of the interlobular septa and the bronchovascular bundles with patchy airspace opacities. Fig. 10: Random micronodular pattern - differential diagnosis Page 15 of 22

16 Fig. 11: Miliary tuberculosis. Innumerable micronodules spread uniformly throughout the lung parenchyma symmetrically without a definable distribution. Fig. 12: Diferential diagnosis of the centrilobular diseases with tree-in-bud Page 16 of 22

17 Fig. 13: Endobronchial tuberculosis. Centrilobular nodules and micronodules. Page 17 of 22

18 Fig. 14: Infectious bronchiolitis. Centrilobular micronodules and linear branching opacities with tree-in-bud sign. Page 18 of 22

19 Fig. 15: Diferential diagnosis of the centrilobular diseases without tree-in-bud Page 19 of 22

20 Fig. 16: Hypersensitivity micronodules. pneumonitis. Ill-defined ground-glass centrilobular Fig. 17: Respiratory bronchiolitis. Centrilobular micronodules and patchy ground-glass opacities. Page 20 of 22

21 Conclusion The differential diagnosis of the micronodular lung pattern includes an extensive list of diseases. Identifying the predominant distribution of the micronodules in HRCT, with the help of the clinical history and eventually other radiological findings is possible narrow or even make an etiologic diagnosis. References 1. Hansell DM, Bankier AA, MacMahon H, McLoud TC, Muller NL, Remy J. Fleischner Society: Glossary of Terms for Thoracic Imaging. Radiology: Volume 246: Number 3-March Michael B. Gotway, Gautham P. Reddy, W. Richard Webb, Brett M. Elicker, Jessica W.T. Leung. High-Resolution CT of the Lung: Patterns of Disease and Differential Diagnoses. Radiol Clin N Am 43 (2005) Webb R. Thin-Section CT of the Secondary Pulmonary Lobule: Anatomy and the Image- The 2004 Fleischner Lecture. Radiology: Volume 239: Number 2-May Raoof S, Amchentsev A, Vlahos I, Goud A, Naidich DP. Pictorial Essay: Multinodular Disease A High-Resolution CT Scan Diagnostic Algorithm. (CHEST 2006; 129: ) 5. Andreu J, Mauleón S, Pallisa E, Majó J, Martinez-Rodriguez, Cáceres J. Miliary Lung Disease Revisited. Curr Probl Diagn Radiol 2002;31: Boitsios G, Bankier AA, Eisenberg RL. Diffuse Pulmonary Nodules. AJR 2010; 194:W354-W Criado E, Sánchez M, Ramírez J, Arguis P, Caralt TM, Perea RJ, Xaubet A. Pulmonary Sarcoidosis: Typical and Atypical Manifestations at High- Resolution CT with Pathologic Correlation. RadioGraphics 2010; 30: Christina Mueller-Mang, Claudia Grosse, Katharina Schmid, Leopold Stiebellehner, Alexander A. Bankier, What Every Radiologist Should Know about Idiopathic Interstitial Pneumonias, RadioGraphics 2007; 27: Johkoh T, Ikezoe J, Tomiyama N, et al. CT findings in lymphangitic carcinomatosis of the lung: correlation with histologic findings and pulmonary function tests. AJR Am J Roentgenol 1992; 158: Santiago Enrique Rossi, Tomas Franquet, Mariano Volpacchio, Ana Gimenez, Gabriel Aguilar, Tree-in-Bud Pattern at Thin-Section CT of the Lungs: Radiologic-Pathologic Overview, RadioGraphics 2005; 25: Gruden J, Webb R, Naidich D, McGuinness G. Multinodular Disease: Anatomic Localization at Thin-Section CT-Multireader Evaluation of a Simple Algorithm. Radiology 1999; 210: Page 21 of 22

22 Personal Information Page 22 of 22