Mimics in chest disease: interstitial opacities
- First Online:
- Cite this article as:
- Oikonomou, A. & Prassopoulos, P. Insights Imaging (2013) 4: 9. doi:10.1007/s13244-012-0207-7
- 5.3k Views
Septal, reticular, nodular, reticulonodular, ground-glass, crazy paving, cystic, ground-glass with reticular, cystic with ground-glass, decreased and mosaic attenuation pattern characterise interstitial lung diseases on high-resolution computed tomography (HRCT). Occasionally different entities mimic each other, either because they share identical HRCT findings or because of superimposition of patterns. Idiopathic pulmonary fibrosis (IPF), fibrosis associated with connective tissue disease, asbestosis, end-stage sarcoidosis or chronic hypersensitivity pneumonitis (HP) may present with lower zone, subpleural reticular pattern associated with honeycombing. Lymphangiomyomatosis may be indistinguishable from histiocytosis or extensive emphysema. Both pulmonary oedema and lymphangitic carcinomatosis may be characterised by septal pattern resulting from thickened interlobular septa. Ill-defined centrilobular nodular pattern may be identically present in HP and respiratory bronchiolitis–associated with interstitial lung disease (RBILD). Sarcoidosis may mimic miliary tuberculosis or haematogenous metastases presenting with miliary pattern, while endobronchial spread of tuberculosis may be indistinguishable from panbronchiolitis, both presenting with tree-in-bud pattern. Atypical infection presenting with ground-glass mimics haemorrhage. Ground-glass pattern with minimal reticulation is seen in desquamative interstitial pneumonia (DIP), RBILD and non-specific interstitial pneumonia (NSIP). Obliterative bronchiolitis and panlobular emphysema may present with decreased attenuation pattern, while obliterative bronchiolitis, chronic pulmonary embolism and HP may manifest with mosaic attenuation pattern. Various mimics in interstitial lung diseases exist. Differential diagnosis is narrowed based on integration of predominant HRCT pattern and clinical history.
• To learn about the different HRCT patterns, which are related to interstitial lung diseases.
• To be familiar with the more “classical” entities presenting with each HRCT pattern.
• To discuss possible overlap of different HRCT patterns and the more common mimics in each case.
• To learn about some clues that help differentiate the various diagnostic mimics on HRCT.
KeywordsInterstitial lung diseasesHRCT patternsMimicsReticularNodularGround-glass opacityCystic
Since the advent of high-resolution computed tomography (HRCT) in the 1990s the understanding of interstitial lung disease has dramatically changed. As CT descriptions of the various diffuse lung diseases are being continuously refined and certain CT characteristics are considered pathognomonic while others become less specific, HRCT finds its role in an integrated approach of diagnosis where it provides sufficient information to produce a differential diagnosis and in many cases allows a non-invasive definitive diagnosis .
There are various patterns of interstitial lung disease on HRCT, each one representing different interstitial lung diseases with completely different histological appearances and clinical manifestations. The main distinct interstitial HRCT patterns are five: septal, reticular, nodular, cystic, ground-glass and decreased lung attenuation pattern. Although each HRCT pattern encompasses many different interstitial lung entities, the contrary may also occur, namely one entity may present with many different patterns and have many different “faces”. To make things even more complicated, there may be overlap of HRCT patterns in one entity. In everyday clinical practice one should try to combine the different HRCT patterns or identify the predominant pattern in order to make the correct diagnosis [2, 3]. Integration of HRCT findings with clinical findings and the knowledge of acute or chronic symptoms is crucial to reach the correct diagnosis.
HRCT patterns and differential diagnosis of interstitial lung diseases
DIFFERENTIAL DIAGNOSIS OF DISEASES
Hydrostatic pulmonary oedema, lymphangitic carcinomatosis, sarcoidosis, Niemann-Pick disease, Erdheim-Chester disease, cystic lymphangiectasia, pulmonary lymphangiomatosis
IPF, NSIP, asbestosis, chronic HP, rheumatoid arthritis, DIP, end-stage sarcoidosis
Subacute HP, RBILD, DIP, Pneumocystis pneumonia
Crazy paving pattern
Alveolar proteinosis, Pneumocystis pneumonia, exogenous lipoid pneumonia, sarcoidosis, diffuse alveolar haemorrhage, viral/opportunistic infection, invasive mucinous adenocarcinoma
Mixed GGO and reticular
NSIP, scleroderma, IPF, DIP
Haematogenous metastases, miliary infection
Sarcoidosis, silicosis, coal workers pneumoconiosis
silicosis, coal workers pneumoconiosis
Panbronchiolitis, tuberculosis, atypical mycobecteria infection, metastatic tumour emboli
Subacute HP, RBILD, cryptogenic organising pneumonia, lymphocytic interstitial pneumonia, follicular bronchiolitis
Sarcoidosis, berylliosis, lymphangitic carcinomatosis
Lymphangioleiomyomatosis, pulmonary histiocytosis, lymphocytic interstitial pneumonia, centrilobular emphysema
Mixed Cystic and GGO
Pneumocystis pneumonia, lymphocytic interstitial pneumonia, subacute HP, DIP
Obliterative bronchiolitis, panlobular emphysema
Obliterative bronchiolitis, chronic thromboembolic pulmonary hypertension, subacute HP, RBILD
For the easier approach to this review by the reader, we describe a “classic” entity and the various “mimics” for each HRCT pattern. The “classic” entity is selected in an arbitrary way either because it may be the most representative and commonly one reported for the specific HRCT pattern or because it may be the entity for which, the specific HRCT pattern was initially described.
Septal pattern is defined as thickening of the interlobular septae (i.e. the borders of the secondary pulmonary lobules). Normally very few interlobular septae are seen in the anterior and lower aspects of the lower lobes on HRCT. Thickened interlobular septae are demonstrated as short lines extending perpendicularly to the peripheral pleura or the fissures, or as polygonal arcades surrounding secondary pulmonary lobules more centrally. Septal thickening can be smooth, nodular or irregular .
There are many “mimics” of the septal pattern: lymphangitic carcinomatosis, sarcoidosis and Niemann-Pick disease, Erdheim-Chester disease, cystic lymphangiectasia and occasionally pulmonary fibrosis.
On HRCT, reticular pattern is characterised by innumerable interlacing shadows suggesting a mesh. The constituents of the reticular pattern may be all or some of the following: interlobular septal thickening, intralobular interstitial thickening, wall cysts of honeycombing, peribronchovascular interstitial thickening and traction bronchiectasis/bronchiolectasis .
The prototype entity for reticular pattern is idiopathic pulmonary fibrosis, which is characterised by subpleural and posterior predominance of intralobular interstitial thickening, traction bronchiectasis/bronchiolectasis, irregular interlobular septal thickening and honeycombing. Areas of ground-glass opacity associated with bronchiectasis and bronchiolectasis may also coexist, but areas of pure ground-glass opacity are extremely rare.
The major mimics of idiopathic pulmonary fibrosis and therefore of reticular pattern are non-specific interstitial pneumonia (NSIP), asbestosis, chronic hypersensitivity pneumonitis, rheumatoid arthritis, desquamative interstitial pneumonia (DIP) and end-stage sarcoidosis.
Ground-glass pattern on HRCT is defined as hazy increase in opacity with preservation of bronchial and vascular markings. Whatever the cause may be—i.e. the partial filling of airspaces, the interstitial thickening, the partial collapse of alveoli or the increased capillary blood volume—they all lead to partial displacement of air .
The most common “mimics” of ground-glass pattern are respiratory bronchiolitis-associated interstitial lung disease (RB-ILD), desquamative interstitial pneumonia (DIP), and Pneumocystis pneumonia.
Desquamative interstitial pneumonia (DIP) typically manifests with diffuse ground-glass opacity as the primary pattern with a subpleural and lower lung predominance. A mild subpleural reticular pattern may be seen in half of the cases. Honeycombing and traction bronchiectasis are minimal—if any. Centrilobular emphysema is also seen in DIP as in RBILD, but mild lower zone reticulation is probably more often expected in DIP rather than RBILD . History of smoking should accompany a diagnosis of DIP as it is almost invariably associated with cigarette smoking.
Crazy paving pattern
“Crazy paving” pattern is characterised on HRCT by the presence of thickened interlobular septae and intralobular lines superimposed on a background of ground-glass opacity, resembling irregularly shaped paving stones .
The most commonly encountered mimics of “crazy paving” pattern are Pneumocystis pneumonia, exogenous lipoid pneumonia, sarcoidosis, diffuse alveolar haemorrhage, viral and opportunistic infections and invasive mucinous adenocarcinoma.
Pneumocystis pneumonia may mimic alveolar proteinosis—although it may rarely present with “crazy paving” pattern as the predominant pattern, especially at the resolving or subacute stage . Histological features contributing to the ground-glass attenuation are the foamy nature of the alveolar exudates and the thickening of the alveolar walls by oedema and cellular infiltrates . Clues that are in favour of Pneumocystis pneumonia may be the coexistence of upper lobe lung cysts, and the knowledge of the stage of the disease during treatment.
Although exogenous lipoid pneumonia (ELP) typically presents with consolidation, that is typically low in attenuation (−100 HU), it may also manifest with geographic areas of ground-glass attenuation surrounded by interlobular septal thickening, representing a “crazy paving” pattern. In terms of HRCT, distinctive features that favour lipoid pneumonia over alveolar proteinosis are the presence of ill-defined centrilobular nodules and the coexistence of consolidation . Transbronchial biopsy, bronchoalveolar lavage and a history of oil ingestion are usually diagnostic for ELP.
Viral and opportunistic infections (adenovirus, herpes simplex, influenza virus, cytomegalovirus, respiratory syncytial virus and toxoplasmosis) in immunocompromised patients may commonly manifest with “crazy paving pattern”, as the predominant pattern. Key finding in these cases is the knowledge of immunosuppression from the clinical history .
Mixed ground-glass–reticular pattern
Occasionally, there may be coexistence of ground-glass pattern and reticular pattern—as defined earlier—in the same areas of the lungs and this combination is invariably equal to the presence of irreversible fibrosis .
The most clinically important mimics of mixed ground-glass–reticular pattern are scleroderma, idiopathic pulmonary fibrosis (IPF) and desquamative interstitial pneumonia (DIP).
A nodular pattern is characterised on HRCT by the presence of numerous rounded opacities that range from 2 mm to 1 cm in diameter, with micronodules defined as smaller than 3 mm in diameter . The differential diagnosis—apart from the clinical setting and the ancillary findings—is largely based on the three different patterns of anatomic distribution: perilymphatic, random, and centrilobular. The perilymphatic distribution is characterised by presence of nodules along the peribronchovascular interstitium, interlobular septa and subpleural areas. Random distribution demonstrates nodules without any particular site predominance. Centrilobular nodules are located several millimetres away from the pleural surfaces, interlobar fissures or interlobular septa. Centrilobular distribution further divides into nodules with and without tree-in-bud distribution. Moreover centrilobular nodules without any “tree-in-bud” pattern may be either of homogeneous density or of ground-glass texture.
Lymphangitic carcinomatosis and lymphoproliferative diseases, such as lymphoma, may present with perilymphatic nodules but this does not usually constitute their predominant HRCT pattern and they are accompanied by other findings such as septal thickening (in the former case) and large parenchymal nodules or masses (in the latter case) that help in the differential diagnosis [3, 41].
The most commonly encountered mimics of nodular pattern with random distribution are miliary metastatic disease, as well as other miliary infections such as miliary candidiasis .
Nodular—centrilobular with tree-in-bud pattern
The tree-in-bud pattern represents centrilobular branching structures that resemble a budding tree. The pattern reflects a spectrum of endobronchiolar and peribronchiolar disorders, including mucoid impaction, inflammation, fibrosis and occasionally endovascular disorders such as neoplastic processes.
The most clinically important mimics of nodular with centrilobular tree-in-bud pattern are endobronchial spread of tuberculosis, atypical mycobacteria infection and metastatic tumour emboli.
Metastastatic tumour emboli in pulmonary arterioles may also present with a “tree-in-bud” pattern, which in this case refers to the vascular rather than the bronchial tree. It is either caused by the filling of the centrilobular arteries with tumour emboli or by the fibrocellular intimal hyperplasia induced by tumour microemboli. Ancillary findings may be the multifocal dilatation and beading of arteries, the thickening of the interlobular septae and small wedge-shaped peripheral opacities, secondary to microinfarcts .
Nodular—ill-defined centrilobular (without tree-in-bud) pattern
This pattern is characterised by the presence of poorly defined centrilobular nodules of ground-glass attenuation that appear from the pleural surface, fissures or interlobular septa by several millimetres [4, 41].
The most commonly encountered mimics of nodular ill-defined centrilobular pattern are respiratory bronchiolitis–associated with interstitial lung disease (RBILD), cryptogenic organising pneumonia, lymphocytic interstitial pneumonia and follicular bronchiolitis.
Lymphocytic interstitial pneumonia (LIP) and follicular bronchiolitis may both present with centrilobular micronodules of ground-glass attenuation as the predominant pattern and mimic subacute hypersensitivity pneumonitis. They are considered to represent two ends of a spectrum, with follicular bronchiolitis localised more to the peribronchiolar region and with LIP being more diffuse in the secondary pulmonary lobule. In case of LIP distinctive findings on HRCT may be the associated thickening of the interlobular septae, thin-walled lung cysts, areas of ground-glass opacity and slightly enlarged mediastinal lymphadenopathy. A significant clue from the clinical history is that both entities are strongly associated with underlying autoimmune disease or immunodeficiency, Sjogren’s syndrome, dysproteinaemia or AIDS [58, 59].
A reticulonodular pattern is characterised by the co-occurrence of reticular and micronodular patterns. The micronodules may either be located at the centre of the reticular elements (centrilobular micronodules) or on the linear opacities representing septal or peribronchovascular micronodules .
Berylliosis is the most important mimic of sarcoidosis on imaging and cannot be distinguished from it even on histological basis. Its main HRCT manifestations are the co-occurrence of perilymphatic nodules, thickening of interlobular septa and peribronchovascular interstitial thickening . Lymphadenopathy is expected to be less pronounced than sarcoidosis and the main key finding to reach the correct diagnosis seem to rest on the knowledge of history of exposure.
Lymphangitic carcinomatosis may occasionally present with a reticulonodular pattern characterised by irregular, nodular thickening of the interlobular septae and of the bronchovascular bundles. Differentiating CT findings from sarcoidosis are the preservation of the architecture of the secondary pulmonary lobule, the more diffuse distribution if it is secondary to extrapulmonary cancer or the confinement to one lobe or lung if it is secondary to lung cancer and the less common incidence of mediastinal lymphadenopathy .
Cystic pattern is composed by well-defined, round and circumscribed air-containing parenchymal spaces with a well-defined wall and interface with normal lung. The wall of the cysts may be uniform or varied in thickness, but usually is thin (<2 mm) and occurs without associated emphysema .
The most clinically important mimics of cystic pattern are pulmonary histiocytosis, lymphocytic interstitial pneumonia (LIP) and centrilobular emphysema.
Combined cystic and ground-glass pattern
This combined HRCT pattern is characterised by the co-occurrence of two already mentioned HRCT patterns, i.e. the cystic pattern and the ground-glass pattern.
The most clinically important mimics of combined cystic and ground-glass pattern are lymphocytic interstitial pneumonia, subacute hypersensitivity pneumonitis and desquamative interstitial pneumonia.
Subacute hypersensitivity pneumonitis (HP) may also manifest with this combined HRCT pattern as the predominant pattern. However, in case of HP the lung cysts are reported to be few in number and thin-walled . The distinctive HRCT finding is characteristic lobular areas of decreased attenuation, even from the inspiratory images and the absence of smoking history, since smokers very rarely develop HP .
Decreased attenuation pattern
The decreased attenuation pattern is defined as areas of low density corresponding to parenchymal destruction and reduced perfusion, and attenuation of the pulmonary vasculature. It is also known as the “black lung” pattern.
Mosaic attenuation pattern
This pattern is characterised by a patchwork of intermingled areas of increased and decreased attenuation that may represent (1) patchy interstitial disease, (2) obliterative small airways disease and (3) occlusive small vascular disease .
Subacute hypersensitivity pneumonitis may also exhibit a mosaic attenuation pattern, combining both an “interstitial” cause, manifesting as areas of increased attenuation (ground-glass opacity), and a “small airways disease” cause, manifesting as areas of decreased attenuation, which may accentuate on expiratory CT . Respiratory bronchiolitis may also occasionally produce this pattern.
Evaluation of interstitial lung diseases on HRCT is based on an HRCT-pattern approach to diagnosis, where there should be effort to assign the predominant HRCT pattern to each case. There are various mimics in each HRCT pattern and one entity may have many faces and therefore may mimic many patterns. There may also be possible overlap of HRCT patterns in one case. Moreover, we should keep in mind that no HRCT pattern provides a specific etiological diagnosis. In order to reach a correct and confident diagnosis, one should approach the predominant HRCT pattern by identifying any specific and distinctive imaging clues and try to narrow the differential diagnosis by integrating the HRCT findings with the clinical and laboratory findings.
Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.