February 2023 Medical Image of the Month: Reversed Halo Sign in the Setting of a Neutropenic Patient with Angioinvasive Pulmonary Zygomycosis

Figure 1. Axial reconstructions from unenhanced (A) and enhanced (B) chest CTs performed 1 week prior to admission (A) and at admission (B) demonstrating rapid interval increase in size of an initially small left upper lobe nodule (arrow) with extensive central necrosis manifesting as a “reversed halo” sign (circled, B).

Figure 2. Sagittal reconstructions from unenhanced (A, C) and enhanced (B) chest CTs through the left lung performed 1 week prior to admission (A), at admission (B), and 2 weeks after admission (C). Small nodules on initial CT (arrows, A) rapidly grow with prominent central necrosis (circle, B). The follow up CT after the patient started improving demonstrates an “air crescent” sign (arrowhead, C) consistent with improving angioinvasive fungal infection.

Figure 3. Low power view, GMS special stain (A) demonstrating a pulmonary artery with fungal elements invading into the wall and out into the surrounding lung parenchyma. There are variable and broad hyphae, with rare septation, many short fragments compatible with Rhizopus species grown in fungal culture. Low power view, H & E stain (B) from a different portion of the sample demonstrating fungal hyphae and spores with thinner morphology, right angle-branching, and calcium oxalate crystals, morphologically compatible with Aspergillus. This may represent secondary colonization of damaged lung.

A 66-year-old man presented to our emergency department with fever and lethargy. A CBC demonstrated profound neutropenia with an absolute neutrophil count of <0.50x10⁹ cells/L (critically low). The patient was admitted and workup for febrile neutropenia was begun. The patient’s past medical history includes CLL (recently confirmed to be in remission by bone marrow biopsy), hypogammaglobulinemia/capillary leak syndrome (presumably related to obinutuzumab therapy, for which patient receives monthly IVIG), and coccidioidomycosis (for which the patient has been followed by infectious disease at our institution, is on fluconazole). An outpatient chest CT performed 1 week prior to presentation to follow up pulmonary nodules demonstrated a few scattered small, but new, inflammatory-appearing nodules (Figure 1A, 2A).

A repeat chest CT was performed at time of admission, 7 days after the initial CT, which demonstrated marked interval increase in size of the small nodules, now represented as large areas of mass-like consolidation including a large finding in the left upper lobe displaying a reversed-halo sign (Figure 1B, 2B). Rapidly progressive fungal infection in the setting of neutropenia was favored. Due to rapid clinical deterioration and development of sites of infection outside the lungs, the decision was made to resect the left upper lobe for source control. The patient tolerated the procedure well, pathology from the specimen demonstrated pulmonary angioinvasive zygomycosis (mucormycosis) with broad areas of hemorrhagic pulmonary infarction, neutrophilic infiltrates and organizing hemorrhagic pneumonia. There were many invasive fungal organisms extending through the infarcted lung tissue. A culture of the lung showed Rhizopus species. There was prominent fungal angioinvasion with thrombosis in and around the infarcted lung. There were additional fungi in a bronchus that were thinner with more spores, septations, and elaborating oxalate crystals that were more consistent with Aspergillus species suggesting polymicrobial fungal infection. The patient was started on amphotericin B and posaconazole as well as filmgastrin. His neutropenia slowly improved, as did his clinical situation. A follow-up CT performed  2 weeks later demonstrated an air-crescent sign in the left lower lobe consistent with improving angioinvasive fungal infection in the setting of resolving neutropenia (Figure 2C). 

The reversed halo sign consists of a finding of peripheral consolidation and central ground glass, in counter distinction to the CT halo sign, which consists of a nodule or mass (or mass-like consolidation) surrounded by ground glass (1). Interestingly, the halo sign was initially described in the setting of angioinvasive aspergillus infection (2), yet the opposite “reversed halo” sign is, in this case and many other cases, also described in the setting of invasive pulmonary fungal infection (3). The reversed halo sign was classically described in the setting of cryptogenic organizing pneumonia (4), where there is central disease clearing. This sign is also described as the “atoll” sign (5), representing relatively normal, improving lung in that situation. In the setting of invasive fungal infection, the central ground glass represents the opposite situation: dead, necrotic lung rather than improving lung. Although organizing pneumonia and invasive fungal infection are well-recognized causes of the reversed halo sign, the sign is by no means specific. Reversed halo signs can be seen in a wide variety of pathologies including paracoccidioidomycosis, pneumocystis pneumonia, tuberculosis, community-acquired pneumonia, lymphomatoid granulomatosis, granulomatosis with polyangiitis, lipoid pneumonia, sarcoidosis, pulmonary infarction, post-radiofrequency ablation and more (6).

Clinton Jokerst MD¹, Yasmeen Butt MD², Ann McCullough MD², Carlos Rojas MD¹, Prasad Panse MD¹, Kris Cummings MD¹, Eric Jensen MD¹ and Michael Gotway MD¹

Departments of Radiology¹

Mayo Clinic Arizona, Scottsdale, AZ USA

Departments of Pathology²

Mayo Clinic Arizona, Scottsdale, AZ USA

References

1. Hansell DM, Bankier AA, MacMahon H, McLoud TC, Müller NL, Remy J. Fleischner Society: glossary of terms for thoracic imaging. Radiology. 2008 Mar;246(3):697-722. [CrossRef] [PubMed]
2. 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 Dec;157(3):611-4. [CrossRef] [PubMed]
3. Wahba H, Truong MT, Lei X, Kontoyiannis DP, Marom EM. Reversed halo sign in invasive pulmonary fungal infections. Clin Infect Dis. 2008 Jun 1;46(11):1733-7. [CrossRef] [PubMed]
4. Kim SJ, Lee KS, Ryu YH, Yoon YC, Choe KO, Kim TS, Sung KJ. Reversed halo sign on high-resolution CT of cryptogenic organizing pneumonia: diagnostic implications. AJR Am J Roentgenol. 2003 May;180(5):1251-4. [CrossRef] [PubMed]
5. Zompatori M, Poletti V, Battista G, Diegoli M. Bronchiolitis obliterans with organizing pneumonia (BOOP), presenting as a ring-shaped opacity at HRCT (the atoll sign). A case report. Radiol Med. 1999 Apr;97(4):308-10. [PubMed]
6. Godoy MC, Viswanathan C, Marchiori E, Truong MT, Benveniste MF, Rossi S, Marom EM. The reversed halo sign: update and differential diagnosis. Br J Radiol. 2012 Sep;85(1017):1226-35. [CrossRef] [PubMed]

Cite as: Jokerst C, Butt Y, McCullough A, Rojas C, Panse P, Cummings K, Jensen E, Gotway M. February 2023 Medical Image of the Month: Reversed Halo Sign in the Setting of a Neutropenic Patient with Angioinvasive Pulmonary Zygomycosis. Southwest J Pulm Crit Care Sleep. 2023;26(2):21-23. doi: https://doi.org/10.13175/swjpccs003-23 PDF

Medical Image of the Month: Radiation-induced Organizing Pneumonia

Figure 1. Axial contrast enhanced CT depicting marked skin thickening of the right breast with fibrotic changes in the adjacent costal lung parenchyma.

Figure 2. Axial/Coronal CT images in lung window showing central ground glass attenuation with surrounding consolidation areas in both lung fields involving regions beyond the radiation field.

Radiotherapy post breast conserving surgery has been in vogue for the treatment of early breast cancer. Organizing pneumonia is one of the responses the lung has to acute lung injury. However, an unusual organizing pneumonia is being recognized with peculiarity of involving the lung zones beyond the actual irradiated parenchyma. Clinically patients may be asymptomatic or present with fever, nonproductive cough, dyspnea, malaise, fatigue and weight loss. The “reverse halo” sign describes the central ground glass haze surrounded by consolidation. Subsequent imaging may reveal migratory infiltrates.

The recognition of this entity is important as a differential with a good prognosis. Though the response to steroids is marked, radiation-induced organizing pneumonia can quickly relapse once the steroid is withdrawn (1,2).

Saika Amreen MD, Nidha Nazir MBBS, Naseer A. Choh MD, and Tariq Gojwari MD.

Department of Radiodiagnosis

Sher-i-Kashmir Institute of Medical Sciences (SKIMS)

Soura, Srinagar, India

References

1. Takigawa N, Segawa Y, Saeki T, et al. Bronchiolitis obliterans organizing pneumonia syndrome in breast-conserving therapy for early breast cancer: radiation-induced lung toxicity. Int J Radiat Oncol Biol Phys. 2000 Oct 1;48(3):751-5. [CrossRef] [PubMed]
2. Otani K, Seo Y, Ogawa K. Radiation-induced organizing pneumonia: a characteristic disease that requires symptom-oriented management. Int J Mol Sci. 2017 Jan 27;18(2). pii: E281. [CrossRef] [PubMed]

Cite as: Amreen S, Nazir N, Choh NA, Gojwari T. Medical image of the month: radiation-induced organizing pneumonia. Southwest J Pulm Crit Care. 2019;19(6):167-8. doi: https://doi.org/10.13175/swjpcc014-19 PDF

Medical Image of the Week: Pulmonary Infarction- the “Reverse Halo Sign”

Figure 1. CT Chest with contrast. Two different levels in the same patient displayed on mediastinal windows. Several triangular shaped subpleural lesions with annular peripheral solid appearance are depicted, better characterized in the lung windows below (yellow arrows). Note the partial filling defect (red arrow on B), indicating a non-occlusive thrombus(arrow). Bilateral pleural effusions are also identified.

Figure 2. CT Chest with contrast, lung window corresponding to the levels in Figure 1 above. Note the triangular shaped subpleural lesions with peripheral solid appearance and ground glass center, characteristic of the atoll sign (arrows). As above, bilateral pleural effusions are present.

Pulmonary infarction is a known complication of pulmonary embolism (PE), a common disorder that results in 100,000-200,000 deaths annually in the United States. Computed tomography (CT) is the first-line modality to assess the pulmonary circulation with the ability to directly the visualize pulmonary emboli as well as pleuro-parenchymal abnormalities.

The appearance of a pulmonary infarct varies depending on the degree of ischemic injury in the setting of a dual blood supply to the lung. Infarcts occur more commonly in the periphery of the lung, given, the alternate blood supply by the bronchial arteries, is not as efficient as it is centrally. This location is also favored by the more common occurrence after occlusion of small peripheral arteries of 3 mm or less in caliber.

On CT lung infarcts can take the can take the “reverse halo” sign, also known as the “atoll” sign configuration, representing a focal area of decreased enhancement, and surrounding solid appearance. In the case of lung infarcts, the lesions typically have a broad pleural base triangular form with apex toward the hilum (1). Pathologically this corresponds to a hemorrhagic consolidation. The center of the lesion appears to correspond to aerated non-infarcted lung coexisting side by side with infarcted lung in the same lobule. The broad-based configuration is explained by the fan shaped distribution of the arteries as they extend out into the periphery. The convex border reflects the extravasated blood within the infarcted lung. Once the hemorrhage reabsorbs, the infarct heals completely or may leave behind a linear band of scarring.

From the imaging stand point, the reverse halo sign initially described in cryptogenic organizing pneumonia, has also been noted in patients with fungal disease, granulomatosis with polyangiitis, sarcoidosis and neoplastic disease among others (2).

George R Wu MS IV¹, Berndt Schmit MD², Veronica Arteaga MD², and Diana Palacio MD²

¹Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ USA

²Division of Thoracic Imaging, University of Arizona, Tucson, AZ USA

References

1. He H, Stein MW, Zalta B, Haramati LB. Pulmonary infarction: spectrum of findings on multidetector helical CT. J Thorac Imaging. 2006;21(1):1-7. [CrossRef] [PubMed]
2. Godoy MC, Viswanathan C, Marchiori E, et al. The reversed halo sign: update and differential diagnosis. Br J Radiol. 2012;85(1017):1226-35. [CrossRef] [PubMed]

Cite as: Wu GR, Schmit B, Arteaga V, Palacio D. Medical image of the week: pulmonary infarction- the “reverse halo sign”. Southwest J Pulm Crit Care. 2017;15(4):162-3. doi: https://doi.org/10.13175/swjpcc124-17 PDF 

Medical Image of the Week: The Atoll Sign in Cryptogenic Organizing Pneumonia

Figure 1. Portable chest X-ray shows bilateral airspace opacities (yellow arrows) and possible trace pleural effusion (blue arrow).

Figure 2. Computed tomography of the chest showing (A) patchy ground glass opacity in the upper lungs with additional scattered circular areas of opacity in a reverse halo configuration (blue arrows, atoll sign) and (B) extensive bibasilar consolidation with air bronchograms.

A 54-year-old woman presented to the emergency department with cough and worsening shortness of breath. Her cough began approximately 1 month prior to presentation, at which time she was diagnosed with pneumonia by her primary care physician based on a chest X-ray at an outside institution. She tried and failed courses of azithromycin, doxycycline, and levofloxacin.

The patient had an oxygen saturation of 55% and hyperpyrexia to 101.7 F in the emergency department. An initial chest X-ray was suggestive of moderate multifocal pneumonia with pleural effusion (Figure 1). Subsequent chest computed tomography (CT; Figure 2) revealed findings consistent with cryptogenic organizing pneumonia (COP) including multiple upper lobe atoll signs. Infectious and autoimmune workups were negative and the patient experienced a rapid recovery with pulse steroids, providing further evidence for the diagnosis of COP.

CT is the best imaging modality for evaluation of potential COP. Features include consolidations and nodules, bronchial wall thickening or dilatation, and ground glass opacities (1). The atoll sign, consisting of a central ground glass opacity and surrounding consolidation which may also be called a reverse halo sign, is highly specific but not sensitive for organizing pneumonia (2). Definitive diagnosis requires lung biopsy, although the disease is often managed based on a presumptive diagnosis (3).

Joseph Frankl, BS¹ and Veronica A. Arteaga, MD²

¹University of Arizona College of Medicine and ²Department of Medical Imaging

Banner University Medical Center Tucson

Tucson, AZ USA

References

1. Lee JW, Lee KS, Lee HY, Chung MP, Yi CA, Kim TS, Chung MJ. Cryptogenic organizing pneumonia: serial high-resolution CT findings in 22 patients. AJR Am J Roentgenol. 2010 Oct;195(4):916-22. [CrossRef] [PubMed]
2. Davidsen JR, Madsen HD, Laursen CB. Reversed halo sign in cryptogenic organising pneumonia. BMJ Case Rep. 2016 Feb 8;2016. pii: bcr2015213779. [CrossRef] [PubMed]
3. Bradley B, Branley HM, Egan JJ, et al. Interstitial lung disease guideline: the British Thoracic Society in collaboration with the Thoracic Society of Australia and New Zealand and the Irish Thoracic Society. Thorax. 2008 Sep;63 Suppl 5:v1-58. [CrossRef] [PubMed]

Cite as: Frankl J, Artega VA. Medical image of the week: the atoll sign in cryptogenic organizing pneumonia. Southwest J Pulm Crit Care. 2017;15(2):92-3. doi: https://doi.org/10.13175/swjpcc100-17 PDF