Figure 1
Chest X-ray
+1 day HCT. PA (a) and lateral (b) chest X-ray. Pseudonodular consolidation (white arrow) on the right upper lobe (RUL).
The Reversed Halo Sign in Pulmonary Mucormycosis with cerebral dissemination in immunocompromised host.
SectionChest imaging
Case TypeClinical Cases
AuthorsE. Cruces Fuentes, A. Sánchez González, I. Vicente Zapata, IM. González Moreno, I. Cases Susarte, JM. Plasencia Martínez
Connected authors
57 years, male
Clinical History
A 57-year-old man underwent allogeneic haematopoietic stem cell transplant (HCT) for primary myelofibrosis. The patient presented severe neutropenia and received prophylaxis to prevent graft-versus-host-disease. On the same day of the infusion, spiking of fevers began that did not remit despite broad-spectrum antibiotics.
Imaging Findings
The chest radiography in the third day after HCT (Fig. 1) revealed a pseudonodular consolidation on the right upper lobe (RUL), which progressed after empirical antibiotic therapy (Fig. 2).
An enhancement thoracic CT was performed and a rounded area of airspace consolidation accompanied by central (“reversed halo" sign) and peripheral (“halo sign”) ground-glass opacity was found in the RUL.
The broncoloalveolar lavage (BAL) isolated the typical hyphae of mucormycosis [1].
After 6 days of HCT, the patient presented nasal stuffiness and brain CT demonstrated a hypodense lesion in right frontal lobe with loss of the cortical–subcortical differentiation suggestive of septic embolism (Fig. 4). There were no lesions of the nasal cavity and paranasal sinuses. Although the patient was asymptomatic neurologically, control enhanced brain CT demonstrated a cerebral abscess formation in the same place as the previous lesion (Fig. 5).
An enhancement thoracic CT was performed and a rounded area of airspace consolidation accompanied by central (“reversed halo" sign) and peripheral (“halo sign”) ground-glass opacity was found in the RUL.
The broncoloalveolar lavage (BAL) isolated the typical hyphae of mucormycosis [1].
After 6 days of HCT, the patient presented nasal stuffiness and brain CT demonstrated a hypodense lesion in right frontal lobe with loss of the cortical–subcortical differentiation suggestive of septic embolism (Fig. 4). There were no lesions of the nasal cavity and paranasal sinuses. Although the patient was asymptomatic neurologically, control enhanced brain CT demonstrated a cerebral abscess formation in the same place as the previous lesion (Fig. 5).
Discussion
Mucormycosis infection is caused by fungi of the class Zygomycetes, most commonly the order Mucorales [2]. This is an opportunistic infection, often fatal clinically, typically in immunocompromised patients such as those with diabetes mellitus, haematologic malignancies, or those that have undergone transplantation [3].
The symptoms of pulmonary mucormycosis include fever, dyspnoea, cough and chest pain.
The right lung is more commonly involved than left, and there is a predilection for the involvement of the upper lobes [2, 1].
The radiological manifestations including a variety of findings: lobar consolidation,
isolated mass, nodular disease and cavitation [4-5].
Recently the "reversed halo" sign has been demonstrated as a fairly specific sign of mucormycosis in the correct clinical setting. The reversed halo sign is a focal rounded area of ground-glass opacity surrounded by a crescent or complete ring of consolidation. In contrast to cryptogenic organizing pneumonia (COP), the peripheral capsule in the reverse halo sign tends to be thicker [6–8].
In immunocompromised patients, the halo sign (ground-glass opacity surrounding a pulmonary nodule or mass) and "reversed halo" sign are highly suggestive of early infection by an angioinvasive fungus. The halo sign is most commonly associated with invasive pulmonary aspergillosis and reversed halo sign with pulmonary mucormycosis [6] (Fig. 6).
Pulmonary mucormycosis in neutropenic patients has the highest incidence of dissemination, although haematogenous dissemination may originate from any primary site of infection.
The most common site of dissemination is the brain, as in our case.
In the present case report, haematogenous spread from pulmonary mucormycosis was followed by cerebral fungal embolism and cerebral abscess. The mortality associated with dissemination to the brain approaches 100%. Cerebral mucormycosis usually manifests as rhino-cerebral mucormycosis where lesions of the nasal cavity and paranasal sinuses extend to the adjacent central nervous system [9].
The management of pulmonary mucormycosis is a combination of surgical and medical treatment. Amphotericin B remains the gold standard antifungal agent used against mucormycosis. Combined surgical/medical treatment may provide a better survival outcome than medical therapy alone [2]. Our patient was treated with liposomal amphotericin B and caspofungin, however, he did not improve and he died.
Mucormycosis prognosis is poor, the overall mortality is approximately 50-70% but increases to 95% with extrathoracic dissemination [2].
Take home points:
In a situation of neutropenia, the "reversed halo" sign should make us suspect a mucormycosis, especially if the standard antifungal therapy is not effective.
The symptoms of pulmonary mucormycosis include fever, dyspnoea, cough and chest pain.
The right lung is more commonly involved than left, and there is a predilection for the involvement of the upper lobes [2, 1].
The radiological manifestations including a variety of findings: lobar consolidation,
isolated mass, nodular disease and cavitation [4-5].
Recently the "reversed halo" sign has been demonstrated as a fairly specific sign of mucormycosis in the correct clinical setting. The reversed halo sign is a focal rounded area of ground-glass opacity surrounded by a crescent or complete ring of consolidation. In contrast to cryptogenic organizing pneumonia (COP), the peripheral capsule in the reverse halo sign tends to be thicker [6–8].
In immunocompromised patients, the halo sign (ground-glass opacity surrounding a pulmonary nodule or mass) and "reversed halo" sign are highly suggestive of early infection by an angioinvasive fungus. The halo sign is most commonly associated with invasive pulmonary aspergillosis and reversed halo sign with pulmonary mucormycosis [6] (Fig. 6).
Pulmonary mucormycosis in neutropenic patients has the highest incidence of dissemination, although haematogenous dissemination may originate from any primary site of infection.
The most common site of dissemination is the brain, as in our case.
In the present case report, haematogenous spread from pulmonary mucormycosis was followed by cerebral fungal embolism and cerebral abscess. The mortality associated with dissemination to the brain approaches 100%. Cerebral mucormycosis usually manifests as rhino-cerebral mucormycosis where lesions of the nasal cavity and paranasal sinuses extend to the adjacent central nervous system [9].
The management of pulmonary mucormycosis is a combination of surgical and medical treatment. Amphotericin B remains the gold standard antifungal agent used against mucormycosis. Combined surgical/medical treatment may provide a better survival outcome than medical therapy alone [2]. Our patient was treated with liposomal amphotericin B and caspofungin, however, he did not improve and he died.
Mucormycosis prognosis is poor, the overall mortality is approximately 50-70% but increases to 95% with extrathoracic dissemination [2].
Take home points:
In a situation of neutropenia, the "reversed halo" sign should make us suspect a mucormycosis, especially if the standard antifungal therapy is not effective.
Differential Diagnosis List
Pulmonary mucormycosis with cerebral dissemination.
Differential diagnosis of halo sign and reversed halo sign (Fig. 6)
-
Final Diagnosis
Pulmonary mucormycosis with cerebral dissemination.
References
[1] Walsh TJ, Gamaletsou MN, McGinnis MR, Hayden RT, Kontoyiannis DP. (2012) Early clinical and laboratory diagnosis of invasive pulmonary, extrapulmonary, and disseminated mucormycosis (zygomycosis). Clin Infect Dis 54 (Suppl 1): S55-S60 (PMID: 22247446)
[2] Spellberg B, Edwards J, Ibrahim A. (2005) Novel perspectives on mucormycosis: Pathophysiology, presentation, and management. Clinical Microbiology Reviews 18 (3): 556-69 (PMID: 16020690)
[3] Pagano L, Offidani M, Fianchi L, Nosari A, Candoni A, Picardi M, et al. (2004) Mucormycosis in hematologic patients. Haematologica 89: 207-14 (PMID: 15003897)
[4] Wang X, Guo L, Xue S, Chen Y. (2016) Pulmonary mucormycosis: A case report and review of the literature. Oncol Lett 22;11(5):3049–53 (PMID: 27123061)
[5] Horger M, Hebart H, Schimmel H, Vogel M, Brodoefel H, Oechsle K, et al. (2006) Disseminated mucormycosis in haematological patients: CT and MRI findings with pathological correlation. Br J Radiol 79:e88–95 (PMID: 27123061)
[6] Georgiadou SP, Sipsas N V., Marom EM, Kontoyiannis DP. (2011) The diagnostic value of halo and reversed halo signs for invasive mold infections in compromised hosts. Clin Infect Dis 52(9):1144–55. (PMID: 21467021)
[7] Godoy M, Viswanathan C, Marchiori E, Truong MT, Benveniste MF, Rossi S, et al. (2012) The reversed halo sign: Update and differential diagnosis. Br J Radiol 85:1226–35. (PMID: 22553298)
[8] Marchiori E, Zanetti G, Hochhegger B, Irion KL, Carvalho ACP, Godoy MCB. (2012) Reversed halo sign on computed tomography: State-of-the-art review. Lung 190: 389-94 (PMID: 22573292)
[9] Higo T, Kobayashi T, Yamazaki S, Ando S, Gonoi W, Ishida M, et al. (2015) Cerebral embolism through hematogenous dissemination of pulmonary mucormycosis complicating relapsed leukemia. Int J Clin Exp Pathol 8(10):13639–42 (PMID: 26722589)
Case information
| URL: | https://eurorad.org/case/14502 |
| DOI: | 10.1594/EURORAD/CASE.14502 |
| ISSN: | 1563-4086 |
License
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Figure 2
Chest X-ray
+3 days HCT. PA (a) and lateral (b) chest X-ray. Evolution of the nodular opacity (white arrow) with an increase of density and size.
Figure 3
Chest CT
Axial (a), sagittal (b) and coronal (c) chest CT demonstrate a pulmonary mass with three components: central ground glass opacity (“reversed halo sign”) (*) and peripheral (arrow) ground glass opacity (halo sign) and intermedial consolidation.
Figure 4
Brain CT
+6 days HCT. Axial non-enhanced brain CT scan shows corticosubcortical hypoattenuation in the right frontal lobe which suggests a septic embolism, with a lineal hyperdensity that could indicate a minimal petechial haemorrhage (arrow).
Figure 5
Brain CT
+22 days HCT. Axial enhanced brain CT scan shows a brain abscess with enhanced peripheral rim and vasogenic oedema associated, which is causing mass effect and shift of midline structures.
Figure 6
The CT Halo Sign and Reversed Halo Sign: differential diagnosis.
Differential diagnosis of halo sign and reversed halo sign.
Chest X-ray
+1 day HCT. PA (a) and lateral (b) chest X-ray. Pseudonodular consolidation (white arrow) on the right upper lobe (RUL).
Department of Radiology, Hospital Universitario Morales Meseguer, Murcia, Spain
Department of Radiology, Hospital Universitario Morales Meseguer, Murcia, Spain
Chest X-ray
+3 days HCT. PA (a) and lateral (b) chest X-ray. Evolution of the nodular opacity (white arrow) with an increase of density and size.
Department of radiology, Hospital Universitario Morales Meseguer, Murcia, Spain.
Department of radiology, Hospital Universitario Morales Meseguer, Murcia, Spain.
Chest CT
Axial (a), sagittal (b) and coronal (c) chest CT demonstrate a pulmonary mass with three components: central ground glass opacity (“reversed halo sign”) (*) and peripheral (arrow) ground glass opacity (halo sign) and intermedial consolidation.
Department of radiology, Hospital Universitario Morales Meseguer, Murcia, Spain.
Department of radiology, Hospital Universitario Morales Meseguer, Murcia, Spain.
Brain CT
+6 days HCT. Axial non-enhanced brain CT scan shows corticosubcortical hypoattenuation in the right frontal lobe which suggests a septic embolism, with a lineal hyperdensity that could indicate a minimal petechial haemorrhage (arrow).
Department of radiology, Hospital Universitario Morales Meseguer, Murcia, Spain.
Department of radiology, Hospital Universitario Morales Meseguer, Murcia, Spain.
Brain CT
+22 days HCT. Axial enhanced brain CT scan shows a brain abscess with enhanced peripheral rim and vasogenic oedema associated, which is causing mass effect and shift of midline structures.
Department of radiology, Hospital Universitario Morales Meseguer, Murcia, Spain.
Department of radiology, Hospital Universitario Morales Meseguer, Murcia, Spain.
The CT Halo Sign and Reversed Halo Sign: differential diagnosis.
Differential diagnosis of halo sign and reversed halo sign.
Department of Radiology, Hospital Universitario Morales Meseguer, Murcia, Spain
Department of Radiology, Hospital Universitario Morales Meseguer, Murcia, Spain