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

March 2016 Imaging Case of the Month

Michael B. Gotway, MD

Department of Radiology

Mayo Clinic Arizona

Scottsdale, AZ USA

Imaging Case of the Month CME Information  

Members of the Arizona, New Mexico, Colorado and California Thoracic Societies and the Mayo Clinic are able to receive  0.25 AMA PRA Category 1 Credits™. Completion of an evaluation form is required to receive credit and a link is provided on the last panel of the activity.

0.25 AMA PRA Category 1 Credit(s)™

Estimated time to complete this activity: 0.25 hours

Lead Author(s): Michael B. Gotway, MD. All Faculty, CME Planning Committee Members, and the CME Office Reviewers have disclosed that they do not have any relevant financial relationships with commercial interests that would constitute a conflict of interest concerning this CME activity. 

Learning Objectives:
As a result of this activity I will be better able to:    

1. Correctly interpret and identify clinical practices supported by the highest quality available evidence.
2. Will be better able to establsh the optimal evaluation leading to a correct diagnosis for patients with pulmonary, critical care and sleep disorders.
3. Will improve the translation of the most current clinical information into the delivery of high quality care for patients.
4. Will integrate new treatment options in discussing available treatment alternatives for patients with pulmonary, critical care and sleep related disorders.

Learning Format: Case-based, interactive online course, including mandatory assessment questions (number of questions varies by case). Please also read the Technical Requirements.

CME Sponsor: University of Arizona College of Medicine at the Arizona Health Sciences Center.

Current Approval Period: January 1, 2015-December 31, 2016

Financial Support Received: None.

Clinical History: A 66 year-old man with orthotopic heart transplantation 1 year previously presented with complaints of recent-onset small volume (<1 teaspoon) hemoptysis, post-nasal drip, and night sweats. The patient indicated he had recent contact with several young grandchildren who had upper respiratory tract symptoms. The patient’s past medical history was remarkable for recurrent constrictive pericarditis (surgically treated), hypertension, type II diabetes mellitus (treated with insulin), psoriasis, sleep-disordered breathing, and grade 2 cardiac transplant rejection diagnosed 6 months earlier. The patient’s medication list included insulin, Cellcept (mycophenolate mofetil), Prograf (tacrolimus), prednisone, among others. On physical examination, the patient was mildly tachycardic (heart rate = 104 beats/minute) with an oxygen saturation on room air of 92%. The white blood cell count was within the normal range, but C-reactive protein and B-type natriuretic peptide levels were reportedly elevated.

Frontal chest radiography (Figure 1) was performed, with a radiograph from one month other also shown for comparison.

Figure 1. Frontal (A) chest radiography shows interval development of a thick-walled left lower lobe cavity since a chest radiograph performed one month previously.

Which of the following statements regarding the chest radiograph is most accurate? (Click on the correct answer to proceed to the second of eight panels)

1. The frontal chest radiograph shows a new lung cavity
2. The frontal chest radiograph shows basal predominant fibrotic abnormalities
3. The frontal chest radiograph shows large lung volumes with a cystic appearance
4. The frontal chest radiograph shows new peribronchial lymph node enlargement
5. The frontal chest radiograph shows new poorly defined nodular opacities bilaterally

Cite as: Gotway MB. March 2016 imaging case of the month. Southwest J Pulm Crit Care. 2016(Mar);12(3):90-101. doi: http://dx.doi.org/10.13175/swjpcc023-16 PDF