Brazilian Journal of Pulmonology

ISSN (on-line): 1806-3756 | ISSN (printed): 1806-3713


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Current Issue: 2016 - Volume 42 - Number 6 (November/December)


The halo sign: HRCT findings in 85 patients

Sinal do halo: achados de TCAR em 85 pacientes


Giordano Rafael Tronco Alves1; Edson Marchiori1; Klaus Irion2; Carlos Schuler Nin3; Guilherme Watte3; Alessandro Comarú Pasqualotto3; Luiz Carlos Severo3; Bruno Hochhegger1; 3


1. Programa de Pós-Graduação em Medicina (Radiologia), Universidade Federal do Rio de Janeiro, Rio de Janeiro (RJ) Brasil.
2. Radiology Department, Liverpool Heart and Chest Hospital, Liverpool, United Kingdom.
3. Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre (RS) Brasil.
Submitted: 28 February 2016.
Accepted: 21 July 2016.
Study carried out at the Irmandade da Santa Casa de Misericórdia de Porto Alegre, Porto Alegre (RS) Brasil.

Correspondence to:
Giordano Rafael Tronco Alves. Avenida Roraima, 1000, CEP 97105-900, Santa Maria, RS, Brasil.
Tel.: 55 55 9729-1990. E-mail:
Financial support: None.



Objective: The halo sign consists of an area of ground-glass opacity surrounding pulmonary lesions on chest CT scans. We compared immunocompetent and immunosuppressed patients in terms of halo sign features and sought to identify those of greatest diagnostic value. Methods: This was a retrospective study of CT scans performed at any of seven centers between January of 2011 and May of 2015. Patients were classified according to their immune status. Two thoracic radiologists reviewed the scans in order to determine the number of lesions, as well as their distribution, size, and contour, together with halo thickness and any other associated findings. Results: Of the 85 patients evaluated, 53 were immunocompetent and 32 were immunosuppressed. Of the 53 immunocompetent patients, 34 (64%) were diagnosed with primary neoplasm. Of the 32 immunosuppressed patients, 25 (78%) were diagnosed with aspergillosis. Multiple and randomly distributed lesions were more common in the immunosuppressed patients than in the immunocompetent patients (p < 0.001 for both). Halo thickness was found to be greater in the immunosuppressed patients (p < 0.05). Conclusions: Etiologies of the halo sign differ markedly between immunocompetent and immunosuppressed patients. Although thicker halos are more likely to occur in patients with infectious diseases, the number and distribution of lesions should also be taken into account when evaluating patients presenting with the halo sign.



Objetivo: O sinal do halo consiste em uma área de opacidade em vidro fosco ao redor de lesões pulmonares em imagens de TC de tórax. Pacientes imunocompetentes e imunodeprimidos foram comparados quanto a características do sinal do halo a fim de identificar as de maior valor diagnóstico. Métodos: Estudo retrospectivo de tomografias realizadas em sete centros entre janeiro de 2011 e maio de 2015. Os pacientes foram classificados de acordo com seu estado imunológico. Dois radiologistas torácicos analisaram os exames a fim de determinar o número de lesões e sua distribuição, tamanho e contorno, bem como a espessura do halo e quaisquer outros achados associados. Resultados: Dos 85 pacientes avaliados, 53 eram imunocompetentes e 32 eram imunodeprimidos. Dos 53 pacientes imunocompetentes, 34 (64%) receberam diagnóstico de neoplasia primária. Dos 32 pacientes imunodeprimidos, 25 (78%) receberam diagnóstico de aspergilose. Lesões múltiplas e distribuídas aleatoriamente foram mais comuns nos imunodeprimidos do que nos imunocompetentes (p < 0,001 para ambas). A espessura do halo foi maior nos imunodeprimidos (p < 0,05). Conclusões: As etiologias do sinal do halo em pacientes imunocompetentes são bastante diferentes das observadas em pacientes imunodeprimidos. Embora halos mais espessos ocorram mais provavelmente em pacientes com doenças infecciosas, o número e a distribuição das lesões também devem ser levados em conta na avaliação de pacientes que apresentem o sinal do halo.



Keywords: Tomography, X-ray computed; Aspergillosis; Lung neoplasms.


Palavras-chave: Tomografia computadorizada por raios X; Aspergilose; Neoplasias pulmonares.




The CT halo sign consists of an area of ground-glass opacity surrounding a pulmonary nodule or mass.(1) The halo sign was first described in 1985 by Kuhlman et al., who reviewed chest CT scans of nine patients with acute leukemia who developed invasive pulmonary aspergillosis. (2) Since then-and despite its infrequency-the halo sign has been reported in association with a variety of conditions.(3,4) Its pathophysiology usually involves one of three mecha-nisms: hemorrhage, inflammation, or neoplastic growth.(5)

Most of the available information about the halo sign has been derived from patients with pre-existing conditions. However, there are limited data on its potential usefulness in predicting the final diagnosis (or diagnostic group, e.g., infection or malignancy). Therefore, the objective of the present study was to determine the diagnostic value of the halo sign by exploring associations between CT measurements and immunological status in a cohort of patients presenting with the CT halo sign.


This was a multicenter retrospective study of CT images obtained between January of 2010 and May of 2014 from patients presenting at any of seven tertiary care centers in southern Brazil, which is an endemic area for granuloma-tous diseases. Scans were selected by searching the picture archiving and communication systems (PACSs) of all participating institutions using the terms "halo" and "halo sign", as well as the following combinations of terms: "ground-glass" + "nodule"; "nodule" + "surround"; "nodule" + "periphery"; and "ground-glass" + "periphery". The research protocol was approved by the local research ethics committee (Protocol no. 243.155). Given the retrospec-tive nature of the study, informed consent was waived.

A general radiologist reviewed the files retrieved from the PACSs in order to confirm the presence of the halo sign. Medical records were reviewed in order to determine patient immune status. For the purpose of the present study, patients were considered immunosuppressed in the presence of AIDS; any form of congenital immunodeficiency; or a recent (≤ two-month) history of chemotherapy, radiation therapy, or decreased white blood cell count (lymphope-nia [absolute lymphocyte count ≤ 1.0 × 109 L] or neutropenia [absolute neutrophil count ≤ 1.5 × 109 L]).(6,7) All other patients were considered to be immunocompetent. If a final diagnosis had not been reached by the time of medical record review, patients were followed until a definitive diagnosis was made, with serological, histological, or micro-biological confirmation. Histological sampling varied across the participating institutions, including transthoracic needle biopsy, video-assisted thoracotomy, and open thoracotomy. Although serological and microbiological tests were performed in accordance with the corresponding (updated) guidelines, their performance was dependent on patient clinical background.

All CT scans were performed with multidetector scanners with at least 16 rows of detectors, the acquisition parame-ters being as follows: slice thickness, ≤ 1.25 mm; rotation time, 0.5 s; voltage, 120 kV; and electric current, 150-400 mA. Automatic exposure control was enabled. No contrast medium was used.

For each examination, the number of lesions, as well as their outline (regular vs. irregular), size, and distribution, together with any other associated findings, were recorded. The criteria for CT findings were those defined in the Fleischner Society Glossary of Terms.(1) A nodule was defined as a rounded or irregular opacity that was well or poorly defined and ≤ 3 cm in diameter. Mediastinal and hilar lymph nodes range in size from sub-CT resolution to 10 mm. A cavity was defined as a gas-filled space, seen as a lucency or low-attenuation area within a pulmonary con-solidation, mass, or nodule. The tree-in-bud pattern refers to centrilobular branching structures that resemble a bud-ding tree. Ground-glass opacities were defined as hazy areas of increased opacity or attenuation with no obscuration of the underlying vessels. Consolidation was defined as homogeneous opacification of the parenchyma with obscura-tion of the underlying vessels. Abnormalities were classified as being located in the upper lobes, located in the lower lobes, or randomly distributed.

The CT scans were independently reviewed in random order by two chest radiologists who had more than 10 years of experience and who were blinded to patient clinical information. Subsequently, the two aforementioned radiolo-gists and a third chest radiologist (with more than 40 years of experience) together reviewed the scans in order to make a final consensus decision. The diameters of the nodules and halos were measured at their widest points on axial CT scans with lung window settings.

Microsoft Excel was used for data storage and descriptive analysis, and the Statistical Package for the Social Sci-ences, version 14.0 (SPSS Inc., Chicago, IL, USA), was used for correlations. The chi-square test was used for quali-tative variables. The Kolmogorov-Smirnov test was used in order to determine whether quantitative data were nor-mally distributed. For parametric variables, the Student's t-test was used. For nonparametric variables, the Mann-Whitney U test was used. All tests were two-tailed, and a significance level of 0.05 was used throughout.


Of the 20,210 CT examinations retrieved from the PACSs of the participating centers, 85 cases (0.42%) were se-lected for inclusion in the present study. Of those 85 patients, 46 were male. In addition, 32 were classified as being immunosuppressed at the time of CT examination, and 53 were immunocompetent. Of those, 34 (64%) were diag-nosed with a primary malignancy; of those, 24 had histopathologically confirmed adenocarcinoma. Of the 32 patients who were classified as being immunosuppressed, 25 (78%) had findings suggestive of invasive aspergillosis (posi-tive results on direct mycological examination or histological findings). All but one of the immunosuppressed patients presenting with invasive aspergillosis were found to have neutropenia. In addition, 7 of those 25 were diagnosed with proven invasive fungal disease (on the basis of specimen culture results and radiological findings), and 18 were diagnosed with probable invasive aspergillosis (on the basis of positive microbiological studies and radiological findings).(8) Other causes of the CT halo sign included metastases, lymphoproliferative diseases, tuberculosis, plasmacytoma, staphylococcal pneumonia, actinomycosis, cryptococcosis, and histiocytosis. Table 1 and Figure 1 show the frequencies of these diagnoses in the two study groups.

The number and distribution of lesions on CT scans were found to vary significantly according to patient immune status, with immunosuppressed patients tending to exhibit multiple and randomly distributed lesions (Table 2). In cases of multiple lesions, halo thickness tended to be greater (≥ 9 mm) in immunosuppressed patients (p < 0.05; Figure 2); the same was not true for single lesions (p = 0.299).


The present retrospective study revealed ten different etiologies of the CT halo sign in 85 individuals. Pathological findings of tumor cells, inflammatory infiltrates, and, most commonly, alveolar hemorrhage have been reported to account for the ground-glass opacities surrounding pulmonary lesions on CT scans. (4,9) Although the halo sign has been causally associated with numerous other conditions, its presence is generally more helpful than challenging. (9) Studies involving immunocompromised patients have confirmed the diagnostic value of the halo sign, demonstrating that its specificity increases as patient immune status deteriorates.(10,11) However, most available evidence consists of descriptive data. To our knowledge, the present study was the first to address the correlations between the halo sign and patient immune status. In addition, our study demonstrated that thicker halos are associated with infectious dis-eases, whereas thinner halos are associated with neoplastic diseases. In agreement with the results of previous studies, the results of the present study showed that adenocarcinoma and pulmonary aspergillosis were the condi-tions that were most commonly associated with the halo sign in immunocompetent and immunosuppressed patients, respectively.(4,12) In cases of multiple pulmonary nodules, halo thickness tended to be greater in immunocompro-mised patients than in immunocompetent patients. This finding is consistent with those of a study investigating char-acteristics of the reversed halo sign, in which greater rim thickness was associated with invasive fungal infection.(13) The same cannot be concluded for solitary nodules, and this is possibly due to a statistically insufficient number of single lesions among the immunosuppressed patients (i.e., only three).

According to Gao et al., the relationships between ground-glass lung nodules and adjacent blood vessels can aid in establishing a final diagnosis based on the presence and degree of vascular distortion.(14) This is particularly relevant for immunocompetent patients presenting with the CT halo sign. In the present study, a neoplastic etiology was found to be more common in the immunocompetent patients than in the immunosuppressed patients. However, given the reduced halo thickness in the former and the variety of possible pathophysiological mechanisms underlying the halo sign, further studies are needed in order to determine whether this correlation can be extrapolated to smaller areas of ground-glass opacities.

Our study has some limitations. First, the retrospective nature of the study increases the likelihood that medical record inaccuracies affected our results. Second, the relatively small sample size did not allow us to perform an analysis of covariance in order to determine the combined contribution of halo sign features in predicting the final diagnosis. Third, dynamic changes observed in the long-term evaluation of the appearance of the halo sign, particu-larly in cases of infectious disease, might have affected some of our results. Finally, the definition of immunosuppres-sion used in our study might be in disagreement with the constant improvements in the toxicity of chemotherapy and radiation therapy; however, that definition was adopted for research purposes only, and many other clinical parame-ters should be taken into account in a more practical scenario.

In summary, our findings are consistent with available data on the etiologies of the CT halo sign in immunocompe-tent and immunosuppressed patients. Given the differences in radiological presentation between these two groups of patients, appropriate assessment of halo sign features can be useful in clinical investigation. A diagnosis of primary neoplasm appears to be common among immunocompetent patients, as does a diagnosis of invasive aspergillosis among immunosuppressed patients. Thicker halos are associated with infectious diseases, whereas thinner halos are associated with neoplastic diseases; the number and distribution of lesions should also be taken into account, given that they can predict the final diagnosis.


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