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

January 2023 Medical Image of the Month: Abnormal Sleep Study and PFT with Supine Challenge Related to Idiopathic Hemidiaphragmatic Paralysis

Figure 1. Results of a sleep study demonstrating a correlation between body position and oxygen saturation.  When the patient moved into right lateral decubitus positioning, their SaO2 dropped (red), when they moved into left lateral decubitus positioning, their SaO2 recovered (Green).  This position-dependent change in SaO2 during sleep suggests right hemidiaphragmatic paralysis.

Figure 2.  Flow-volume loop from pulmonary function testing demonstrates a significant reduction in forced vital capacity (FVC) and forced expiratory volume 1s (FEV1) with supine positioning (green line) compared to upright baseline (red line) suggestive of diaphragmatic dysfunction. 

Figure 3.  Fluoroscopic images from a sniff test at end tidal (A) and “sniffing” (B) portions of exam demonstrating normal depression of the left hemidiaphragm (down arrowhead) and paradoxical elevation of the right hemidiaphragm (up arrowhead) consistent with right hemidiaphragmatic paralysis. Sagittal reconstruction from a noncontrast chest CT (C) demonstrating an elevated but otherwise normal appearing right hemidiaphragm (arrows).

A 71-year-old man presented to our pulmonary clinic with a complaint of worsening dyspnea, which seems to be positional in nature.  Symptoms were exacerbated by bending over or laying down too quickly.  The patient was known to our practice, having had a kidney transplant 17 years ago, a left upper lobectomy for squamous cell carcinoma 6 years ago (no recurrence), and has been on fluconazole for 4 years due to disseminated coccidioidomycosis (cocci) with cavitary pulmonary involvement.  The patient had recurrent DVTs 2 years ago and is on Eliquis.  On top of that, the patient had COVID 1 year ago, but had recovered.  An outside sleep study was remarkable for overnight hypoxia.  Outside pulmonary function testing (PFTs) demonstrated a combined restrictive and obstructive picture.  An outside chest CT failed to demonstrate any findings that would suggest COVID-related changes or progression of cocci as a potential cause.  A V/Q scan was low probability for pulmonary embolism.

 The positional nature of the patient’s symptoms and suspicious physical exam findings suggested abnormal diaphragmatic motion as a potential etiology.  The astute pulmonologist ordered a home sleep study to evaluate for any positional nature to the overnight hypoxia (Fig. 1), PFTs with supine challenge (Fig. 2) and a fluoroscopic sniff test to evaluate diaphragmatic motion (Figure 3).  The sleep study did indeed demonstrate a strong correlation between patient position and SaO2 (dropped when right side down or supine).  The PFTs demonstrated a significant drop in pulmonary function with supine challenge.  The sniff test demonstrated an elevated right hemidiaphragm with paradoxical motion during sniffing maneuvers (Fig. 3A,3B).  Results were consistent with right hemidiaphragmatic paralysis.  Of note, several months later repeat PFTs and sniff test demonstrated some interval improvement in right hemidiaphragmatic paralysis suggesting a reversible process, probably inflammatory and perhaps related to a viral neuritis.

Diaphragmatic paralysis can be further categorized into unilateral or bilateral with these entities each having a somewhat different set of potential etiologies. Distinguishing between unilateral vs. bilateral paralysis is important. Potential causes of unilateral hemidiaphragmatic paralysis can be separated into trauma/iatrogenic causes (such as following CABG), compression (such as cervical spondylosis or tumor along phrenic nerve), neuropathic (such as in multiple sclerosis) or inflammation (such as in the setting of a viral neuritis) (1).  Viral neuritis affecting the phrenic nerve has been reported with COVID-19 (2).  Up to 20% of cases of unilateral hemidiaphragmatic paralysis may be considered idiopathic (3).

The diagnostic approach to suspected hemidiaphragmatic paralysis is actually pretty well demonstrated by this case report.  CXR, in combination with physical exam, is often good as an initial screening exam.  Diaphragmatic motion can be assessed with sniff testing using fluoroscopy (or ultrasound if there is a desire to limit exposure to ionizing radiation).  Evaluation for causes of compression can be done with cross-sectional imaging, particularly CT or MRI.  Pulmonary function testing with supine challenge and a sleep study can also provide useful information, as demonstrated by this case.

Clinton Jokerst MD¹, Carlos Rojas MD¹, Michael Gotway MD¹, and Philip Lyng MD²

Department of Radiology¹

Mayo Clinic Arizona, Scottsdale, AZ USA

Division of Pulmonology²

Mayo Clinic Arizona, Scottsdale, AZ USA

References

1. O'Toole SM, Kramer J. Unilateral Diaphragmatic Paralysis. [Updated 2022 Jun 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK557388/ (accessed 12/12/22).
2. FitzMaurice TS, McCann C, Walshaw M, Greenwood J. Unilateral diaphragm paralysis with COVID-19 infection. BMJ Case Rep. 2021 Jun 17;14(6):e243115. [CrossRef] [PubMed]
3. Kokatnur L, Vashisht R, Rudrappa M. Diaphragm Disorders. 2022 Aug 1. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan–. [PubMed] 

Cite as: Jokerst C, Rojas C, Gotway MB, Lyng P. January 2023 Medical Image of the Month: Abnormal Sleep Study and PFT with Supine Challenge Related to Idiopathic Hemidiaphragmatic Paralysis. Southwest J Pulm Crit Care Sleep. 2023;26(1):5-7. doi: https://doi.org/10.13175/swjpccs057-22 PDF