The Reversed Halo Sign on High- Resolution CT in Infectious and Noninfectious Pulmonary Diseases

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1 Cardiopulmonary Imaging Pictorial Essay Marchiori et al. Reversed Halo Sign on HRCT Cardiopulmonary Imaging Pictorial Essay Downloaded from by on 04/01/18 from IP address Copyright RRS. For personal use only; all rights reserved Edson Marchiori 1,2 Gláucia Zanetti 2 Gustavo Souza Portes Meirelles 3 Dante L. Escuissato 4 rthur Soares Souza, Jr. 5 runo Hochhegger 2 Marchiori E, Zanetti G, Meirelles GSP, Escuissato DL, Souza S Jr., Hochhegger Keywords: high-resolution CT, infectious pulmonary diseases, noninfectious pulmonary diseases, reversed halo sign DOI: /JR Received September 10, 2010; accepted after revision November 7, Department of Radiology, Fluminense Federal University, venue Marquês do Paraná, 530, Centro, Niterói, Rio de Janeiro , razil. ddress correspondence to E. Marchiori (edmarchiori@gmail.com). 2 Department of Radiology, University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, razil. 3 Department of Radiology, University Hospital, Federal University of São Paulo, São Paulo, razil. 4 Department of Radiology, Federal University of Parana, Curitiba, razil. 5 Department of Radiology, Faculty of Medicine of Rio Preto, São José do Rio Preto, razil. WE This is a Web exclusive article. JR 2011; 197:W69 W X/11/1971 W69 merican Roentgen Ray Society The Reversed Halo Sign on High- Resolution CT in Infectious and Noninfectious Pulmonary Diseases OJECTIVE. The purpose of this article is to describe diseases that may present with the reversed halo sign on high-resolution CT. We emphasize the tomographic features most frequently associated with this sign and correlate them with histologic findings. CONCLUSION. wide spectrum of infectious and noninfectious diseases may present with the reversed halo sign on chest CT. The nonspecific nature of this sign should not cloud an otherwise fairly straightforward diagnosis, especially when associated background findings are typical. lthough a rigorous analysis of associated CT findings may help with the differential diagnosis, histologic assessment is often needed for a definitive determination of the cause. T he reversed halo sign is a highresolution CT (HRCT) pattern that is defined as a focal, rounded area of ground-glass attenuation surrounded by a ring of denser consolidation that frequently forms a complete ring, although sometimes it can be incomplete. The reversed halo sign was initially described as a relatively specific finding in the diagnosis of cryptogenic organizing pneumonia [1]. Other studies have shown the presence of this sign in a wide spectrum of diseases including infectious conditions such as paracoccidioidomycosis [2], tuberculosis [3], zygomycosis [4], and aspergillosis [4]; and noninfectious conditions including cryptogenic organizing pneumonia [1], Wegener granulomatosis [5], lymphomatoid granulomatosis [6], and sarcoidosis [7] among other processes. Therefore, the reversed halo sign must be regarded as a nonspecific sign that can be encountered in various pulmonary diseases. Occasionally, in infectious disease follow-up, this sign may be seen in secondary organizing pneumonia as a response to the initial infection. The aim of this work is to show and discuss the spectrum of diseases that may present with the reversed halo sign on HRCT in cases in which the final diagnosis has been confirmed by histopathology. Infectious Diseases Pulmonary Paracoccidioidomycosis Paracoccidioidomycosis is the most frequent endemic systemic mycosis in Latin merica. The disease is acquired by inhalation of infectious particles containing Paracoccidioides brasiliensis. The HRCT findings of patients with pulmonary paracoccidioidomycosis include ground-glass attenuation areas, small centrilobular nodules, cavitated nodules, parenchymal bands, and areas of paracicatricial emphysema [2, 8]. Gasparetto et al. [2] found the reversed halo sign in 15 of 148 patients (10%) with proven paracoccidioidomycosis (Fig. 1). Pulmonary Tuberculosis Tuberculosis is an airborne bacterial disease caused by Mycobacterium tuberculosis and is a major infectious cause of morbidity and mortality, particularly in developing countries. Multiple HRCT findings may be seen in patients with a history of primary tuberculosis including centrilobular or airspace nodules and branching linear structures (tree-in-bud pattern), consolidations, cavitations, bronchial wall thickening, miliary nodules, tuberculomas, calcifications, parenchymal bands, interlobular septal thickening, ground-glass opacities, paracicatricial emphysema, and fibrotic changes [3, 9]. Descriptions of the reversed halo sign in tuberculosis are restricted to case reports [3]. n important consideration is that the ring of the reversed halo sign in active granulomatous diseases may be nodular in appearance because of the presence of granulomas [9]. lthough this finding may be an important criterion for the differential diagnosis of organizing pneumonia [9] (Fig. 2), its association with other tomographic signs JR:197, July 2011 W69

2 Marchiori et al. Downloaded from by on 04/01/18 from IP address Copyright RRS. For personal use only; all rights reserved more typical of tuberculosis is the most important factor for the suspicion of the cause of diagnosis. ngioinvasive Pulmonary spergillosis ngioinvasive pulmonary aspergillosis affects almost exclusively immunosuppressed patients, particularly those with marked neutropenia. ngioinvasive aspergillosis is characterized by the presence of single or multiple nodules, typically surrounded by a halo of ground-glass attenuation (CT halo sign), and areas of consolidation or ground-glass opacity. These findings correspond to hemorrhagic infarcts, and cavitation may also occur. During the convalescence phase, fragments of infarcted lung may separate from the adjacent parenchyma (pulmonary sequestra), resulting in a cavity with an air crescent (i.e., the air-crescent sign) [10]. The reversed halo sign (Fig. 3) was described in one patient by Wahba et al. [4]. Pneumocystis jiroveci Pneumonia This form of pneumonia is caused by the fungal microorganism Pneumocystis jiroveci, formerly known as Pneumocystis carinii. The most common HRCT findings are bilateral ground-glass opacities sparing the lung periphery and displaying a mosaic or nearly homogeneous pattern. Less common manifestations include airspace consolidations, patchy linear-reticular opacities, solitary or multiple nodules, parenchymal cystic lesions, and pneumothorax from the rupture of lung cysts to the pleural space. The combination of ground-glass opacities and superimposed intralobular linear opacities results in the crazy paving pattern [11]. To our knowledge, the association of the reversed halo sign with P. jiroveci pneumonia (Fig. 4) has not been previously described. Noninfectious Diseases Cryptogenic Organizing Pneumonia Cryptogenic organizing pneumonia is an uncommon lung disease characterized by the presence of patches of granulation tissue polyps in the interior of the alveoli; in the alveolar ducts; and, to a lesser extent, in the bronchioles (Masson bodies). These polyps are associated with focal organizing pneumonia. The most common HRCT findings are areas of parenchymal consolidation or groundglass attenuation that are most frequently bilateral, are typically in subpleural or peribronchovascular areas, and are predominantly in the lower lobes. Nodules or masses, occasionally with a surrounding halo (i.e., the halo sign), may be seen. The reversed halo sign was initially described as being specific for cryptogenic organizing pneumonia but as being infrequent in this disease (Fig. 5). Other less frequent findings in cryptogenic organizing pneumonia include centrilobular nodules, bronchial dilatation, and interlobular septal thickening [1, 12]. ronchioloalveolar Carcinoma ronchioloalveolar carcinoma is defined as a subtype of adenocarcinoma with intraalveolar spread and lepidic growth along an intact interstitial framework with no evidence of stromal, vascular, or pleural invasion. On HRCT, bronchioloalveolar carcinoma can present as solitary or multiple pulmonary nodules of varying densities, with and without cavitation, air bronchograms, bubblelike lucencies of pseudocavitation, unifocal or multifocal ground-glass opacities, crazy paving pattern, lobar or multilobar consolidation, or a combination of these features [13]. To our knowledge, the association of the reversed halo sign with bronchioloalveolar carcinoma (Fig. 6) has not been previously described. Wegener Granulomatosis Wegener granulomatosis is a multisystem disease of unknown cause characterized by a necrotizing granulomatous vasculitis affecting predominantly the upper and lower respiratory tracts, lung, and kidneys. The absence of necrotizing glomerulonephritis is defined as the limited form and is considered to be early-stage disease. The diagnosis of Wegener granulomatosis is confirmed by antineutrophil cytoplasmic antibodies and biopsy. The HRCT findings consist of lung nodules or masses, ground-glass opacities or consolidations, and airway involvement. Cavitation is common. Consolidations and ground-glass opacities are usually related to hemorrhage [5, 14]. garwal et al. [5] described the reversed halo sign in one patient with Wegener granulomatosis (Fig. 7). Pulmonary Edema Pulmonary edema is a common pathologic condition that basically results from an increase in the pulmonary microvascular pressure, a decrease in plasma oncotic pressure, or an increase in microvascular permeability. These phenomena may occur in isolation or association. The main HRCT findings are ground-glass opacities, interlobular septal thickening, crazy paving pattern, pleural effusion, and peribronchovascular interstitial thickening [15]. Less common findings include increased blood vessel diameter, consolidations, airspace nodules, and the reversed halo sign (Fig. 8). Sarcoidosis Sarcoidosis is a disorder of unknown origin characterized by noncaseating granulomatous inflammation that affects various body sites. The HRCT findings are extremely variable. ilateral hilar lymphadenopathy is the most common feature of sarcoidosis and typically manifests as bilateral hilar and right paratracheal adenopathy. Lung involvement is characterized by the presence of multiple small perilymphatic nodules corresponding to sarcoid granulomas and nodular thickening of the bronchovascular bundles, interlobular septa, pleural surfaces, and interlobar fissures. Other features include bronchial wall thickening, ground-glass attenuation, the reversed halo sign (Fig. 9), and large nodules comprising a coalescence of numerous smaller nodules surrounded by peripheral satellite nodules (previously referred as the sarcoid galaxy sign) [7]. Conclusion wide spectrum of diseases can manifest with the reversed halo sign on chest HRCT. This pattern is most often an indication of cryptogenic organizing pneumonia, but it may also be associated with other conditions such as inflammatory, neoplastic, or infectious diseases. lthough the reversed halo sign is relatively nonspecific, correlation of clinical findings and other HRCT patterns with this finding can sometimes help the physician to narrow the differential diagnosis. ecause cryptogenic organizing pneumonia may be idiopathic or may be secondary to infections, collagen vascular diseases, eosinophilic lung diseases, Wegener granulomatosis, and neoplasms, knowing whether the reversed halo sign is a manifestation of primary disease or secondary organizing pneumonia is difficult. Morphologic aspects of the halo, particularly the presence of small nodules in the wall or inside the lesion, usually indicate an active granulomatous disease (infection or sarcoidosis) rather than a primary cryptogenic organizing pneumonia. References 1. Kim SJ, Lee KS, Ryu YH, et al. Reversed halo sign on high-resolution CT of cryptogenic organizing pneumonia: diagnostic implications. JR W70 JR:197, July 2011

3 Reversed Halo Sign on HRCT Downloaded from by on 04/01/18 from IP address Copyright RRS. For personal use only; all rights reserved 2003; 180: Gasparetto EL, Escuissato DL, Davaus T, et al. Reversed halo sign in pulmonary paracoccidioidomycosis. JR 2005; 184: Marchiori E, Grando RD, Simões Dos Santos CE, et al. Pulmonary tuberculosis associated with the reversed halo sign on high-resolution CT. r J Radiol 2010; 83:e58 e60 4. Wahba H, Truong MT, Lei X, Kontoyiannis DP, Marom EM. Reversed halo sign in invasive pulmonary fungal infections. Clin Infect Dis 2008; 46: garwal R, ggarwal N, Gupta D. nother cause of reverse halo sign: Wegener s granulomatosis. r J Radiol 2007; 80: enamore RE, Weisbrod GL, Hwang DM, et al. Reversed halo sign in lymphomatoid granulomatosis. r J Radiol 2007; 80:e162 e Kumazoe H, Matsunaga K, Nagata N, et al. Reversed halo sign of high-resolution computed tomography in pulmonary sarcoidosis. J Thorac Imaging 2009; 24: Marchiori E, Valiante PM, Mano CM, et al. Paracoccidioidomycosis: high-resolution computed tomography-pathologic correlation. Eur J Radiol 2011; 77:80 84; Epub 2009 Jul Marchiori E, Zanetti G, Hochhegger, Irion KL. Re: reversed halo sign nodular wall as criterion for differentiation between cryptogenic organizing pneumonia and active granulomatous diseases. Clin Radiol 2010; 65: Franquet T, Müller NL, Giménez, Guembe P, de La Torre J, agué S. Spectrum of pulmonary aspergillosis: histologic, clinical, and radiologic findings. RadioGraphics 2001; 21: Luks M, Neff MJ. Pneumocystis jiroveci pneumonia. Respir Care 2007; 52: ravo Soberón, Torres Sánchez MI, García Río F, Sánchez lmaraz C, Parrón Pajares M, Pardo Rodríguez M. High-resolution computed tomography patterns of organizing pneumonia [in Spanish]. rch ronconeumol 2006; 42: Lee KS, Kim Y, Han J, Ko EJ, Park CK, Primack SL. ronchioloalveolar carcinoma: clinical, histopathologic, and radiologic findings. Radio- Graphics 1997; 17: Lohrmann C, Uhl M, Kotter E, urger D, Ghanem N, Langer M. Pulmonary manifestations of Wegener granulomatosis: CT findings in 57 patients and a review of the literature. Eur J Radiol 2005; 53: Gluecker T, Capasso P, Schnyder P, et al. Clinical and radiologic features of pulmonary edema. RadioGraphics 1999; 19: Fig year-old man with pulmonary paracoccidioidomycosis., High-resolution CT scan shows bilateral localized round and oval areas (arrows) containing central ground-glass opacities and ring of consolidation (reversed halo sign). lso seen are small nodules and focal areas of ground-glass attenuation., Photomicrograph (H and E, 100) of middle lobe specimen obtained at biopsy by videothoracoscopy shows that lesions have inflammatory infiltrate in alveolar septa (arrows), with relative preservation of alveolar spaces in central areas, or dense and homogeneous intraalveolar cellular infiltrate in peripheral halo (not shown). C, Photomicrograph (Grocott-Gomori methenamine silver stain, 200) confirms presence of fungus (Paracoccidioides brasiliensis) (arrows). C JR:197, July 2011 W71

4 Marchiori et al. Downloaded from by on 04/01/18 from IP address Copyright RRS. For personal use only; all rights reserved Fig year-old woman with pulmonary tuberculosis., High-resolution CT scan shows bilateral pulmonary opacities with central areas of groundglass attenuation surrounded by denser nodular ring (i.e., reversed halo sign) (arrowheads)., Photomicrograph (H and E, 40) of lingular segment obtained from open lung biopsy shows confluent granulomas on ring wall (asterisks). Fig year-old woman with chronic leukemia and invasive pulmonary aspergillosis., High-resolution CT scan shows bilateral pleural effusion and mass in left lower lobe, with reversed halo sign (arrows)., Photomicrograph (H and E, 40) of left lower lobe specimen obtained at biopsy by videothoracoscopy shows hemorrhage (asterisks) inside mass. C, Photomicrograph (Grocott methenamine silver stain, 40) reveals hyphae of spergillus organisms (arrows) in periphery of lesion that are invading pulmonary parenchyma. C W72 JR:197, July 2011

5 Reversed Halo Sign on HRCT Downloaded from by on 04/01/18 from IP address Copyright RRS. For personal use only; all rights reserved Fig year-old man with IDS and Pneumocystis jiroveci pneumonia., High-resolution CT scan shows multiple areas of reversed halo sign and ground-glass opacities in both lungs., Photomicrograph (H and E, 40) of lingula specimen obtained from biopsy by videothoracoscopy shows partial filling of airspaces (asterisks) by foamy exudate, mainly consisting of surfactant, fibrin, and cellular debris. lso seen is inflammatory infiltrate of alveolar septa (arrows). C, On photomicrograph (Grocott-Gomori methenamine silver stain, 200) of histologic specimen, microorganisms are typically seen by silver stain within exudate (arrows). Lung biopsy could not identify components of dense halo. Fig year-old man with cryptogenic organizing pneumonia., High-resolution CT scan of lower pulmonary regions shows consolidations with reversed halo sign in left lower lobe (arrows)., Photomicrograph (H and E, 40) of left lower lobe specimen obtained at open lung biopsy shows that dense halo is formed by involvement of airspaces by polypoid fibroblastic foci (asterisks) distributed within terminal bronchioles, alveolar ducts, and alveoli. C JR:197, July 2011 W73

6 Marchiori et al. Downloaded from by on 04/01/18 from IP address Copyright RRS. For personal use only; all rights reserved Fig year-old man with bronchioloalveolar carcinoma., High-resolution CT scan shows small nodule in left lower lobe with reversed halo sign (arrowheads)., Photomicrograph (H and E, 100) of left lower lobe specimen obtained at open lung biopsy shows proliferation of tumoral cells lining alveolar wall with preservation of lung architecture (arrowheads). Peripheral halo is formed by dense proliferation of tumoral cells. Fig year-old man with Wegener granulomatosis and hemoptysis., High-resolution CT scan shows multiple pulmonary nodules with reversed halo sign (arrows)., Photomicrograph (H and E, 100) of lingula specimen obtained at biopsy by videothoracoscopy shows that dense halo is formed by inflammatory cell infiltrate accompanied by necrosis involving blood vessels (arrows). Necrotizing vasculitis of small vessel is seen. W74 JR:197, July 2011

7 Reversed Halo Sign on HRCT Downloaded from by on 04/01/18 from IP address Copyright RRS. For personal use only; all rights reserved Fig year-old woman with noncardiogenic pulmonary edema secondary to use of nitrofurantoin for treatment of urinary infection., High-resolution CT scan shows nodular groundglass opacities surrounded by incomplete ring of consolidation., Follow-up CT scan obtained 4 days after after withdrawal of drug, oxygen therapy, and supportive care shows reabsorption of opacities. Fig year-old woman with sarcoidosis., High-resolution CT scan shows bilateral round areas with central ground-glass opacities surrounded by ring-shaped areas of consolidation (arrows). lso noted are small nodules scattered throughout both lungs., Photomicrograph (H and E, 40) of middle lobe specimen obtained at biopsy by videothoracoscopy shows scattered, well-demarcated, nonnecrotizing granulomas (asterisks). Dense halo was formed by higher concentration of granulomas in lesion periphery. JR:197, July 2011 W75