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CT halo sign in cases of pulmonary metastasis from bone or soft tissue sarcoma
ARTICLE IN PRESS Respiratory Medicine Extra (2006) 2, 135–138
respiratory MEDICINE Extra
CASE REPORT
CT halo sign in cases of pulmonary metastasis from bone or soft tissue sarcoma Manabu Hashimotoa,, Etuko Tatea, Jiro Wataraia, Masahiro Sasakib a
Department of Radiology, Akita University School of Medicine, 1-1-1 Hondo, Akita City 010-8543, Japan Department of internal medicine, Akita University School of Medicine, 1-1-1 Hondo, Akita City 010-8543, Japan
b
Received 27 September 2006; accepted 3 November 2006
KEYWORDS CT; Halo; Lung tumor
Summary Aim: We reviewed a series of patients with lung metastases from bone or soft tissue sarcoma to evaluate the frequency of the CT halo sign and CT features of metastatic lesions showing this sign. Methods: The study included 19 patients with lung metastasis from bone or soft tissue sarcoma treated during a 4-year period at our institution. The CT halo sign was defined as a central pulmonary nodule surrounded by a distinct zone of ground-glass opacification (halo). Results: The CT halo sign was found in 4 (21%) of the 19 patients. One of the 4 patients had 2 nodules characterized by the CT halo sign; the others had 1. All 5 nodules with a halo had a well-defined margin. The long axis of the central nodules was 4–78 mm (mean, 25.4 mm). The area of the halo was extensive in 4 small nodules (long axis o25 mm). Histologic examination, performed in 1 case, showed that the halo corresponded to lepidic proliferation of tumor cells. Conclusion: Metastatic nodules from bone or soft tissue sarcoma are sometimes characterized by a CT halo. The halo of small metastatic nodules can be large. & 2006 Elsevier Ltd. All rights reserved.
Introduction The CT halo sign refers to a central pulmonary nodule surrounded by a zone of ground-glass attenuation (halo). This sign was first described in patients with severe Corresponding author. Tel.: +81 018 884 6177;
fax: +81 018 836 2623. E-mail address: [email protected] (M. Hashimoto). 1744-9049/$ - see front matter & 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.rmedx.2006.11.001
neutropenia and aspergillosis.1 The CT halo sign has been regarded to represent hemorrhagic pulmonary nodules, especially in patients with infectious disease.1,2 However, this sign has been shown in relation to hemorrhagic nodules associated with a number of other conditions2–4 and in relation to nonhemorrhagic pulmonary nodules in patients with noninfectious diseases.5–7 Lung metastases from various nonepithelial malignant tumors can also show the CT halo sign.2–4,8–10 Most reports of lung metastasis showing the halo sign have performed to
ARTICLE IN PRESS 136 individual patients, except that of a series of patients with lung metastases from angiosarcoma.5 The purpose of this study was to evaluate the frequency of the CT halo sign and the CT features of metastatic lesions showing this sign in patients with lung metastases from bone or soft tissue sarcoma.
Methods We reviewed CT scans obtained between January 2001 and January 2005 from 19 patients (6 women, 13 men; mean age 37.2 years, range 2–75 years) with metastatic lung tumors from bone or soft tissue sarcoma. The metastatic lung tumors were diagnosed during surgery or autopsy in 6 patients, and on the basis of the clinical course and imaging findings (development of lung nodules in patients with a known primary malignancy) in 13 patients. Histologic examination of resected specimens of the primary lesion revealed osteosarcoma in 6 patients, rhabdomyosarcoma in 4, Ewing tumor in 3, leiomyosarcoma in 2, and other sarcomas in 4. We classified the margins of central nodules with a halo as well defined or ill defined, and we classified areas of groundglass attenuation on CT scans as extensive or narrow. CT was performed with helical CT scanners (Siemens Somatom Plus 4). In all cases, contiguous 8 or 5-mm collimation scans of the entire chest were obtained. Additional thin-section collimation scans were obtained at selected levels in 4 patients with only a few nodules.
M. Hashimoto et al. complained of chest pain and hemoptysis. None of the 4 patients had abnormal laboratory values indicative of infection. All 4 patients had multiple nodules in both lungs. Previously obtained CT scans were available for 3 patients (cases 1–3). Metastatic nodules were not found on CT scans obtained 2–4 months earlier in these 3 patients. One patient had 2 nodules with a halo; the other 3 patients each had 1. The long axis of the central nodules was 4–78 mm (mean, 25.4 mm). The margin of all 5 nodules with a halo appeared well defined on the CT scan. The areas of ground-glass attenuation varied in size. The halo area was extensive in 4 small nodules (long axis o25 mm) (Fig. 2).
Results Four of the 19 patients (21%) had metastatic nodule(s) with a distinct CT halo sign (5 nodules)(Figs. 1 and 2). clinical characteristics and CT findings of these 4 patients are summarized in Table 1. Three of the 4 patients had no respiratory symptoms at the time of CT. One patient (case 4)
Figure 2 A 12-year-old girl with multiple lung metastases from osteosarcoma (case 2). High-resolution CT scan (2 mm thickness) shows an extensive halo of ground-glass attenuation surrounding a small central nodule (4 mm in size).
Figure 1 A 67-year-old man with multiple lung metastases from leiomyosarcoma (case 1). (a) CT scan (5 mm thickness) shows a halo of ground-glass attenuation around a central nodule. (b) Photomicrograph of a pathologic specimen obtained during left upper lobectomy shows surrounding tumor infiltration (arrows) from the main tumor (T) into the alveolar walls and corresponding to the area of ground-glass attenuation.
ARTICLE IN PRESS 137
+ + + + Not available Extensive Extensive Extensive Narrow Well-defined Well-defined Well-defined Well-defined (23 mm) (10, 4 mm) (12 mm) (78 mm) 1 2 1 1 Leiomyosarcoma Osteosarcoma Osteosarcoma Rhabdomyosarcoma 1/67/M 2/12/F 3/68/M 4/27/M
5 4 3 430
New module with hole Enlargement of hole
Underlying disease Cases no./Age (years)/Sex
Table 1
Number of metastatic modules
Number of module(s) with hole (module slice)
Margin of central module
Areas of hole (extensive narrow)
Follow-up CT (within 60 days)
Histologic examination
Leptile growth Not available Not available Not available
CT halo
The remaining large nodule had a narrow halo. Three patients (cases 1–3) underwent follow-up CT 20–60 days after initial CT. Follow-up CT showed an increase in the size of the central nodules and enlargement of the areas of ground-glass attenuation. Three new nodules with the CT halo sign were found in 1 patient (case 2). One patient (case 1) underwent resection of the tumors with a halo immediately after follow-up CT. Histologically, the halo of groundglass attenuation corresponded to surrounding infiltration of tumor cells into the alveolar wall from the central nodule. Three patients (cases 1–3) underwent chemotherapy at our institution. These patients were followed up for 12–19 months. The lung metastasis was progressive in all 3 patients; the size and number of metastases increased. Additional new nodules with a halo were found in 1 of these 3 patients (case 2). The areas of ground-glass attenuation observed upon initial CT scans persisted, but these areas became narrow in relation to the increased size of the central nodules in 2 patients (cases 2 and 3). All 3 patients died between 14 and 24 months (median, 19 months) after the initial diagnosis of lung metastasis.
Discussion The CT halo sign was reported in 6 (25%) of a fairly large series of 24 patients with lung metastasis from angiosarcoma.4 The ground-glass attenuation corresponded to alveolar hemorrhage in these 6 cases. Other reports of individual patients have described that a halo represented alveolar hemorrhage.2,3 In cases of lung metastasis from hypervascular tumors such an angiosarcoma, a halo of ground-glass attenuation can result from peritumoral hemorrhage secondary to the fragility of neovascular tissue.4 The area of ground-glass attenuation can also correspond to lepidic tumor spread of lung metastasis from angiosarcoma10 or extrapulmonary carcinoma.5 The CT halo sign was found in 4 of our 19 patients (21%) with lung metastasis from bone or soft tissue sarcoma. In cases of lung metastasis from extrapulmonary carcinoma, the CT halo sign was present in 2 of 65 (3%) patients with lepidic tumor spread corresponding to the area of groundglass attenuation.5 The halo sign is probably rare in the clinical setting; however, the halo sign is probably more frequently associated with lung metastasis from bone or soft tissue sarcoma than with lung metastasis from extrapulmonary carcinoma. There were no specific CT features for metastatic nodules with a halo. Central nodules had a well-defined and relatively smooth margin in all cases. However, the area of ground-glass attenuation was extensive in comparison to the size of the central nodule, especially when the nodule was small. A halo of ground-glass attenuation may result from peritumoral hemorrhage when a new nodule with the CT halo sign develops within a short period.3 However, a metastatic nodule with an extensive halo appeared within a short time (4 months) in the patient in whom lepidic tumor spread was found in the area of halo of ground-glass attenuation. We think it is difficult to determine on the basis of imaging study whether a halo of ground-glass attenuation consists of hemorrhage or of lepidic tumor spread.
ARTICLE IN PRESS 138 Metastatic lung tumors with a halo of our cases developed and enlarged within a short period. We speculated that the metastatic disease progressed rapidly in patients with the halo sign. Although 1 patient (case 2) died of progressive lung metastasis 14 months after the lung metastasis was first found, the clinical course after development of the lung metastasis with a halo seemed not to be so aggressive in the other 2 patients. It is possible that there is no correlation between development of a metastatic nodule with a halo from bone or soft tissue sarcoma and patient prognosis. There are some limitations to our study. First, results of pathologic analysis, i.e., identification of the underlying cause of the halo were available for only 1 patient. We were unable to determine whether the halo of ground-glass attenuation reflected either hemorrhage or lepidic tumor growth in other nodules. In clinical practice, multiple, round pulmonary nodules are usually treated as metastases in patients with a known primary malignancy; biopsy is not usually performed. It is important to know that both tumor spread and hemorrhage can be the cause of a CT halo. Second, we evaluated prognosis in a very small sample. Furthermore, tumors histologies and chemotherapy regimens differed. More cases are needed to confirm our findings. In conclusion, we herein described 4 cases of lung metastasis from bone or soft tissue sarcoma with the CT halo sign. Lung metastases from these sarcomas are sometimes characterized by a CT halo, and the halo can be quite large in comparison to the size of the central nodule, if the nodule is small.
M. Hashimoto et al.
References 1. Kuhlman JE, Fishman EK, Siegelman SS. Invasive pulmonary aspergillosis in acute leukemia: characteristic findings on CT, the CT halo sign, and the role of CT in early diagnosis. Radiology 1985;157:611–4. 2. Primack SL, Hartman TE, Lee KS, Mu ¨ller NL. Pulmonary nodules and the CT halo sign. Radiology 1994;190:513–5. 3. Tomiyama N, Ikezoe J, Miyamoto M, Nakahara K. CT halo sign in metastasis of osteosarcoma. Am J Roentgenol 1994;162:468. 4. Tateishi U, Hasegawa T, Kusumoto M, Yamazaki N, Iinuma G, Muramatsu Y, et al. Metastatic angiosarcoma of the lung: spectrum of CT findings. Am J Roentgenol 2003;180:1671–4. 5. Gaeta M, Volta S, Scribano E, Loria G, Vallone A, Pandolfo I. Airspace pattern in lung metastasis from adenocarcinoma of the GI tract. J Comput Assist Tomogr 1996;20:300–4. 6. Woodring JH, Bognar B. CT halo sign in pulmonary metastases from mucinous adenocarcinoma of the pancreas. Southern Med J 2001;94:448–9. 7. Gaeta M, Caruso R, Barone M, Volta S, Casablanca G, La Spada F. Ground-glass attenuation in nodular bronchioalveolar carcinoma: CT patterns and prognostic value. J Comput Assist Tomogr 1998;22:215–9. 8. Okita R, Yamashita M, Nakata M, Teramoto N, Bessho A, Mogami H. Multiple ground-glass opacity in metastasis of malignant melanoma diagnosed by lung biopsy. Ann Thorac Surg 2005;79:e1–2. 9. Collins J, Stern EJ. Ground-glass opacity at CT: the ABCs. Am J Roentgenol 1997;169:355–67. 10. Kim Y, Lee KS, Jung KJ, Han J, Kim JS, Suh JS. Halo sign on high resolution CT: findings in spectrum of pulmonary diseases with pathologic correlation. J Comput Assist Tomogr 1999;23:622–6.
respiratory MEDICINE Extra
CASE REPORT
CT halo sign in cases of pulmonary metastasis from bone or soft tissue sarcoma Manabu Hashimotoa,, Etuko Tatea, Jiro Wataraia, Masahiro Sasakib a
Department of Radiology, Akita University School of Medicine, 1-1-1 Hondo, Akita City 010-8543, Japan Department of internal medicine, Akita University School of Medicine, 1-1-1 Hondo, Akita City 010-8543, Japan
b
Received 27 September 2006; accepted 3 November 2006
KEYWORDS CT; Halo; Lung tumor
Summary Aim: We reviewed a series of patients with lung metastases from bone or soft tissue sarcoma to evaluate the frequency of the CT halo sign and CT features of metastatic lesions showing this sign. Methods: The study included 19 patients with lung metastasis from bone or soft tissue sarcoma treated during a 4-year period at our institution. The CT halo sign was defined as a central pulmonary nodule surrounded by a distinct zone of ground-glass opacification (halo). Results: The CT halo sign was found in 4 (21%) of the 19 patients. One of the 4 patients had 2 nodules characterized by the CT halo sign; the others had 1. All 5 nodules with a halo had a well-defined margin. The long axis of the central nodules was 4–78 mm (mean, 25.4 mm). The area of the halo was extensive in 4 small nodules (long axis o25 mm). Histologic examination, performed in 1 case, showed that the halo corresponded to lepidic proliferation of tumor cells. Conclusion: Metastatic nodules from bone or soft tissue sarcoma are sometimes characterized by a CT halo. The halo of small metastatic nodules can be large. & 2006 Elsevier Ltd. All rights reserved.
Introduction The CT halo sign refers to a central pulmonary nodule surrounded by a zone of ground-glass attenuation (halo). This sign was first described in patients with severe Corresponding author. Tel.: +81 018 884 6177;
fax: +81 018 836 2623. E-mail address: [email protected] (M. Hashimoto). 1744-9049/$ - see front matter & 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.rmedx.2006.11.001
neutropenia and aspergillosis.1 The CT halo sign has been regarded to represent hemorrhagic pulmonary nodules, especially in patients with infectious disease.1,2 However, this sign has been shown in relation to hemorrhagic nodules associated with a number of other conditions2–4 and in relation to nonhemorrhagic pulmonary nodules in patients with noninfectious diseases.5–7 Lung metastases from various nonepithelial malignant tumors can also show the CT halo sign.2–4,8–10 Most reports of lung metastasis showing the halo sign have performed to
ARTICLE IN PRESS 136 individual patients, except that of a series of patients with lung metastases from angiosarcoma.5 The purpose of this study was to evaluate the frequency of the CT halo sign and the CT features of metastatic lesions showing this sign in patients with lung metastases from bone or soft tissue sarcoma.
Methods We reviewed CT scans obtained between January 2001 and January 2005 from 19 patients (6 women, 13 men; mean age 37.2 years, range 2–75 years) with metastatic lung tumors from bone or soft tissue sarcoma. The metastatic lung tumors were diagnosed during surgery or autopsy in 6 patients, and on the basis of the clinical course and imaging findings (development of lung nodules in patients with a known primary malignancy) in 13 patients. Histologic examination of resected specimens of the primary lesion revealed osteosarcoma in 6 patients, rhabdomyosarcoma in 4, Ewing tumor in 3, leiomyosarcoma in 2, and other sarcomas in 4. We classified the margins of central nodules with a halo as well defined or ill defined, and we classified areas of groundglass attenuation on CT scans as extensive or narrow. CT was performed with helical CT scanners (Siemens Somatom Plus 4). In all cases, contiguous 8 or 5-mm collimation scans of the entire chest were obtained. Additional thin-section collimation scans were obtained at selected levels in 4 patients with only a few nodules.
M. Hashimoto et al. complained of chest pain and hemoptysis. None of the 4 patients had abnormal laboratory values indicative of infection. All 4 patients had multiple nodules in both lungs. Previously obtained CT scans were available for 3 patients (cases 1–3). Metastatic nodules were not found on CT scans obtained 2–4 months earlier in these 3 patients. One patient had 2 nodules with a halo; the other 3 patients each had 1. The long axis of the central nodules was 4–78 mm (mean, 25.4 mm). The margin of all 5 nodules with a halo appeared well defined on the CT scan. The areas of ground-glass attenuation varied in size. The halo area was extensive in 4 small nodules (long axis o25 mm) (Fig. 2).
Results Four of the 19 patients (21%) had metastatic nodule(s) with a distinct CT halo sign (5 nodules)(Figs. 1 and 2). clinical characteristics and CT findings of these 4 patients are summarized in Table 1. Three of the 4 patients had no respiratory symptoms at the time of CT. One patient (case 4)
Figure 2 A 12-year-old girl with multiple lung metastases from osteosarcoma (case 2). High-resolution CT scan (2 mm thickness) shows an extensive halo of ground-glass attenuation surrounding a small central nodule (4 mm in size).
Figure 1 A 67-year-old man with multiple lung metastases from leiomyosarcoma (case 1). (a) CT scan (5 mm thickness) shows a halo of ground-glass attenuation around a central nodule. (b) Photomicrograph of a pathologic specimen obtained during left upper lobectomy shows surrounding tumor infiltration (arrows) from the main tumor (T) into the alveolar walls and corresponding to the area of ground-glass attenuation.
ARTICLE IN PRESS 137
+ + + + Not available Extensive Extensive Extensive Narrow Well-defined Well-defined Well-defined Well-defined (23 mm) (10, 4 mm) (12 mm) (78 mm) 1 2 1 1 Leiomyosarcoma Osteosarcoma Osteosarcoma Rhabdomyosarcoma 1/67/M 2/12/F 3/68/M 4/27/M
5 4 3 430
New module with hole Enlargement of hole
Underlying disease Cases no./Age (years)/Sex
Table 1
Number of metastatic modules
Number of module(s) with hole (module slice)
Margin of central module
Areas of hole (extensive narrow)
Follow-up CT (within 60 days)
Histologic examination
Leptile growth Not available Not available Not available
CT halo
The remaining large nodule had a narrow halo. Three patients (cases 1–3) underwent follow-up CT 20–60 days after initial CT. Follow-up CT showed an increase in the size of the central nodules and enlargement of the areas of ground-glass attenuation. Three new nodules with the CT halo sign were found in 1 patient (case 2). One patient (case 1) underwent resection of the tumors with a halo immediately after follow-up CT. Histologically, the halo of groundglass attenuation corresponded to surrounding infiltration of tumor cells into the alveolar wall from the central nodule. Three patients (cases 1–3) underwent chemotherapy at our institution. These patients were followed up for 12–19 months. The lung metastasis was progressive in all 3 patients; the size and number of metastases increased. Additional new nodules with a halo were found in 1 of these 3 patients (case 2). The areas of ground-glass attenuation observed upon initial CT scans persisted, but these areas became narrow in relation to the increased size of the central nodules in 2 patients (cases 2 and 3). All 3 patients died between 14 and 24 months (median, 19 months) after the initial diagnosis of lung metastasis.
Discussion The CT halo sign was reported in 6 (25%) of a fairly large series of 24 patients with lung metastasis from angiosarcoma.4 The ground-glass attenuation corresponded to alveolar hemorrhage in these 6 cases. Other reports of individual patients have described that a halo represented alveolar hemorrhage.2,3 In cases of lung metastasis from hypervascular tumors such an angiosarcoma, a halo of ground-glass attenuation can result from peritumoral hemorrhage secondary to the fragility of neovascular tissue.4 The area of ground-glass attenuation can also correspond to lepidic tumor spread of lung metastasis from angiosarcoma10 or extrapulmonary carcinoma.5 The CT halo sign was found in 4 of our 19 patients (21%) with lung metastasis from bone or soft tissue sarcoma. In cases of lung metastasis from extrapulmonary carcinoma, the CT halo sign was present in 2 of 65 (3%) patients with lepidic tumor spread corresponding to the area of groundglass attenuation.5 The halo sign is probably rare in the clinical setting; however, the halo sign is probably more frequently associated with lung metastasis from bone or soft tissue sarcoma than with lung metastasis from extrapulmonary carcinoma. There were no specific CT features for metastatic nodules with a halo. Central nodules had a well-defined and relatively smooth margin in all cases. However, the area of ground-glass attenuation was extensive in comparison to the size of the central nodule, especially when the nodule was small. A halo of ground-glass attenuation may result from peritumoral hemorrhage when a new nodule with the CT halo sign develops within a short period.3 However, a metastatic nodule with an extensive halo appeared within a short time (4 months) in the patient in whom lepidic tumor spread was found in the area of halo of ground-glass attenuation. We think it is difficult to determine on the basis of imaging study whether a halo of ground-glass attenuation consists of hemorrhage or of lepidic tumor spread.
ARTICLE IN PRESS 138 Metastatic lung tumors with a halo of our cases developed and enlarged within a short period. We speculated that the metastatic disease progressed rapidly in patients with the halo sign. Although 1 patient (case 2) died of progressive lung metastasis 14 months after the lung metastasis was first found, the clinical course after development of the lung metastasis with a halo seemed not to be so aggressive in the other 2 patients. It is possible that there is no correlation between development of a metastatic nodule with a halo from bone or soft tissue sarcoma and patient prognosis. There are some limitations to our study. First, results of pathologic analysis, i.e., identification of the underlying cause of the halo were available for only 1 patient. We were unable to determine whether the halo of ground-glass attenuation reflected either hemorrhage or lepidic tumor growth in other nodules. In clinical practice, multiple, round pulmonary nodules are usually treated as metastases in patients with a known primary malignancy; biopsy is not usually performed. It is important to know that both tumor spread and hemorrhage can be the cause of a CT halo. Second, we evaluated prognosis in a very small sample. Furthermore, tumors histologies and chemotherapy regimens differed. More cases are needed to confirm our findings. In conclusion, we herein described 4 cases of lung metastasis from bone or soft tissue sarcoma with the CT halo sign. Lung metastases from these sarcomas are sometimes characterized by a CT halo, and the halo can be quite large in comparison to the size of the central nodule, if the nodule is small.
M. Hashimoto et al.
References 1. Kuhlman JE, Fishman EK, Siegelman SS. Invasive pulmonary aspergillosis in acute leukemia: characteristic findings on CT, the CT halo sign, and the role of CT in early diagnosis. Radiology 1985;157:611–4. 2. Primack SL, Hartman TE, Lee KS, Mu ¨ller NL. Pulmonary nodules and the CT halo sign. Radiology 1994;190:513–5. 3. Tomiyama N, Ikezoe J, Miyamoto M, Nakahara K. CT halo sign in metastasis of osteosarcoma. Am J Roentgenol 1994;162:468. 4. Tateishi U, Hasegawa T, Kusumoto M, Yamazaki N, Iinuma G, Muramatsu Y, et al. Metastatic angiosarcoma of the lung: spectrum of CT findings. Am J Roentgenol 2003;180:1671–4. 5. Gaeta M, Volta S, Scribano E, Loria G, Vallone A, Pandolfo I. Airspace pattern in lung metastasis from adenocarcinoma of the GI tract. J Comput Assist Tomogr 1996;20:300–4. 6. Woodring JH, Bognar B. CT halo sign in pulmonary metastases from mucinous adenocarcinoma of the pancreas. Southern Med J 2001;94:448–9. 7. Gaeta M, Caruso R, Barone M, Volta S, Casablanca G, La Spada F. Ground-glass attenuation in nodular bronchioalveolar carcinoma: CT patterns and prognostic value. J Comput Assist Tomogr 1998;22:215–9. 8. Okita R, Yamashita M, Nakata M, Teramoto N, Bessho A, Mogami H. Multiple ground-glass opacity in metastasis of malignant melanoma diagnosed by lung biopsy. Ann Thorac Surg 2005;79:e1–2. 9. Collins J, Stern EJ. Ground-glass opacity at CT: the ABCs. Am J Roentgenol 1997;169:355–67. 10. Kim Y, Lee KS, Jung KJ, Han J, Kim JS, Suh JS. Halo sign on high resolution CT: findings in spectrum of pulmonary diseases with pathologic correlation. J Comput Assist Tomogr 1999;23:622–6.