Radiological CT Patterns and Distribution of Invasive Pulmonary Aspergillus, Non-Aspergillus, Cryptococcus and Pneumocystis Jirovecii Mold Infections – A Multicenter Study

Abstract

Purpose Clinical signs and symptoms related to invasive fungal disease are nonspecific and need to be followed up by appropriate diagnostic procedures. The goal of this study was to analyze CT imaging patterns in invasive fungal infections and their correlation with the immune status and clinical outcome.

Materials and Methods We performed a retrospective multicenter study including 85 consecutive patients with invasive pulmonary fungal infection (2011–2014). Lung patterns on computed tomography (CT) scans were classified according to the Fleischner Society glossary. The patients were grouped according to immune status (neutropenia, steroid therapy, organ transplant recipient, and other cause) and outcome (positive outcome, progressive disease, and death). The Chi square test or Fisher exact test was used. Bonferroni correction was applied.

Results The total number of patients with invasive Aspergillus and non-Aspergillus infection (IANA), Pneumocystis jirovecii pneumonia (PCP), and Cryptococcus (CRY) was 60, 22, and 3, respectively. Patients with IANA demonstrated significantly more nodules (93 % vs. 59 %, p = 0.001), significantly fewer ground glass opacities (58 % vs. 96 %, p = 0.005), and significantly fewer positive lymph nodes (5 % vs. 41 %, p < 0.001) than patients with PCP. All patients with PCP and CRY had a favorable outcome. Patients with IANA and an adverse outcome demonstrated significantly more nodules with halo sign than patients with IANA and a favorable outcome (42.5 % vs. 15.9 %, p < 0.0001). Interestingly, patients with IANA and a favorable outcome had a higher prevalence of pulmonary infarction than patients with an adverse outcome (8 % vs. 1 %, p = 0.047). Patients with neutropenia showed significantly more consolidations (66 %) than organ transplant recipients (27 %, p = 0.045).

Conclusion Patients with IANA showed a higher prevalence of nodules and a lower prevalence of ground glass opacities than patients with PCP. In patients with IANA, nodules with halo sign were associated with an adverse outcome. Patients with neutropenia showed generally more consolidations, but the consolidations were not associated with an adverse outcome.

Key Points: 

• Nodules, ground glass opacities, and consolidations are common CT findings in all invasive pulmonary fungal infections.

• There is no pattern that is unique for one specific pathogen, although nodules are more predominant in IANA and Cryptococcus, and ground glass opacities are more predominant in PCP patients.

• Immune status had an impact on CT findings in fungal pneumonia with less consolidation in patients after organ transplantation compared to patients with neutropenia.

• Nodules with a halo sign are associated with a worse outcome.

Citation Format

• Obmann VC, Bickel F, Hosek N et al. Radiological CT Patterns and Distribution of Invasive Pulmonary Aspergillus, Non-Aspergillus, Cryptococcus and Pneumocystis Jirovecii Mold Infections – A Multicenter Study. Fortschr Röntgenstr 2021; 193: 1304 – 1314

Zusammenfassung

Ziel Systematische Analyse der CT-Muster bei invasiven pulmonalen Pilzinfektionen in Abhängigkeit vom Immunstatus und dem klinischen Outcome der Patienten.

Material und Methoden In dieser retrospektiven Multicenterstudie wurden 85 konsekutive Patienten mit invasiver pulmonaler Pilzinfektion eingeschlossen (2011–2014). Die CT-Muster der Lunge wurden gemäß dem Glossar der Fleischner-Society klassifiziert. Die Patienten wurden nach Immunstatus (Neutropenie, Steroidtherapie, Organtransplantation und andere Ursachen) und Outcome (positiver Verlauf, progrediente Erkrankung und Tod) unterteilt. Der Chi-Quadrat- und der Fischer-Exact-Test wurden mit der Bonferroni-Korrektur angewandt.

Ergebnisse Die Anzahl der Patienten mit invasiver Aspergillus- und Nicht-Aspergillus-Infektion (IANA), Pneumocystis-jirovecii-Pneumonie (PCP) und Kryptokokken (CRY) betrug jeweils 60, 22 und 3. Die IANA-Patienten wiesen signifikant häufiger Lungenknoten (93 % vs. 59 %; p = 0,001), signifikant weniger Milchglastrübungen (58 % vs. 96 %; p = 0,005) und signifikant weniger pathologische Lymphknoten auf (5 % vs. 41 %; p < 0,001) als Patienten mit PCP. Alle Patienten mit PCP und CRY zeigten einen positiven Verlauf. Bei IANA-Patienten waren Knoten mit Halo-Zeichen häufiger assoziiert mit negativem (Progress, Tod) als mit positivem Verlauf (42,5 % vs. 15,9 %; p < 0,0001). Interessanterweise zeigten Patienten mit positivem Verlauf häufiger Lungeninfarkte als Patienten mit negativem Verlauf (8 % vs. 1 %; p = 0,047). Patienten mit Neutropenie litten signifikant mehr an Lungeninfiltraten (Konsolidierungen, 66 %) als Patienten nach Organtransplantation (27 %; p = 0,045).

Schlussfolgerung IANA-Patienten zeigten eine höhere Prävalenz von Lungenknoten und eine tiefere Prävalenz von Milchglastrübungen im Vergleich zu PCP-Patienten. Bei den IANA-Patienten waren die Noduli mit Halo-Zeichen mit einem schlechteren Verlauf assoziiert. Patienten mit Neutropenie zeigten generell mehr Infiltrate, diese waren allerdings nicht mit negativem Verlauf assoziiert.

Kernaussagen: 

• Lungenknoten, Milchglastrübungen und Konsolidierungen sind häufige CT-Zeichen bei allen invasiven pulmonalen Pilzinfektionen.

• Es gibt kein CT-Muster, das einzigartig ist für einen bestimmten Erreger, obwohl Lungenknoten häufiger bei IANA und Kryptokokken vorkommen und Milchglastrübungen häufiger bei PCP-Infektionen zu beobachten sind.

• Der Immunstatus der Patienten beeinflusst die CT-Befunde der Pilz-Pneumonie: Patienten zeigten nach Organtransplantation weniger Konsolidierungen als Patienten mit Neutropenie.

• Noduli mit Halo-Zeichen sind mit einem schlechteren Outcome assoziiert.

Key words

ultrasound computed tomography (US/CT) - x-ray - invasive fungal infections - chest - pneumonia

Publication History

Received: 01 October 2020

Accepted: 05 April 2021

Article published online:
25 May 2021

• References

• 1 von Eiff M, Roos N, Schulten R. et al. Pulmonary aspergillosis: early diagnosis improves survival. Respiration; international review of thoracic diseases 1995; 62: 341-347
• 2 Mucha K, Foroncewicz B, Orlowski T. et al. Atypical presentation of invasive pulmonary aspergillosis in a liver transplant recipient. Annals of transplantation 2013; 18: 238-242
• 3 Yan C, Tan X, Wei Q. et al. Lung MRI of invasive fungal infection at 3 Tesla: evaluation of five different pulse sequences and comparison with multidetector computed tomography (MDCT). European radiology 2015; 25: 550-557
• 4 Karthaus M, Buchheidt D. Invasive aspergillosis: new insights into disease, diagnostic and treatment. Current pharmaceutical design 2013; 19: 3569-3594
• 5 Walsh TJ, Gamaletsou MN. Treatment of fungal disease in the setting of neutropenia. Hematology American Society of Hematology Education Program 2013; 2013: 423-427
• 6 Lee HJ, Cho SY, Lee DG. et al. Characteristics and risk factors for mortality of invasive non-Aspergillus mould infections in patients with haematologic diseases: A single-centre 7-year cohort study. Mycoses 2020; 63: 257-264
• 7 Agrawal R, Yeldandi A, Savas H. et al. Pulmonary Mucormycosis: Risk Factors, Radiologic Findings, and Pathologic Correlation. Radiographics 2020; DOI: 10.1148/rg.2020190156:190156.
• 8 Kuhlman JE, Fishman EK, Burch PA. et al. Invasive pulmonary aspergillosis in acute leukemia. The contribution of CT to early diagnosis and aggressive management. Chest 1987; 92: 95-99
• 9 Ascioglu S, Rex JH, de Pauw B. et al. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America 2002; 34: 7-14
• 10 De Pauw B, Walsh TJ, Donnelly JP. et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America 2008; 46: 1813-1821
• 11 Ruhnke M, Behre G, Buchheidt D. et al. Diagnosis of invasive fungal diseases in haematology and oncology: 2018 update of the recommendations of the infectious diseases working party of the German society for hematology and medical oncology (AGIHO). Mycoses 2018; 61: 796-813
• 12 Cornely OA, Alastruey-Izquierdo A, Arenz D. et al. Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium. The Lancet Infectious diseases 2019; 19: e405-e421
• 13 Ullmann AJ, Aguado JM, Arikan-Akdagli S. et al. Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline. Clinical microbiology and infection: the official publication of the European Society of Clinical Microbiology and Infectious Diseases 2018; 24 (Suppl. 01) e1-e38
• 14 Lass-Florl C. How to make a fast diagnosis in invasive aspergillosis. Medical mycology 2019; 57: S155-S160
• 15 Godet C, Elsendoorn A, Roblot F. Benefit of CT scanning for assessing pulmonary disease in the immunodepressed patient. Diagnostic and interventional imaging 2012; 93: 425-430
• 16 Wang J, Zhang C, Lin J. et al. Clinical diagnostic value of spiral CT in invasive pulmonary fungal infection. Experimental and therapeutic medicine 2019; 17: 4149-4153
• 17 Legouge C, Caillot D, Chretien ML. et al. The reversed halo sign: pathognomonic pattern of pulmonary mucormycosis in leukemic patients with neutropenia?. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America 2014; 58: 672-678
• 18 Georgiadou SP, Sipsas NV, Marom EM. et al. The diagnostic value of halo and reversed halo signs for invasive mold infections in compromised hosts. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America 2011; 52: 1144-1155
• 19 Hansell DM, Bankier AA, MacMahon H. et al. Fleischner Society: glossary of terms for thoracic imaging. Radiology 2008; 246: 697-722
• 20 Herbrecht R, Denning DW, Patterson TF. et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. The New England journal of medicine 2002; 347: 408-415
• 21 Xu S, Qiu L, Liu W. et al. Initial computed tomography findings of invasive pulmonary aspergillosis in non-hematological patients. Chinese medical journal 2012; 125: 2979-2985
• 22 Park SY, Lim C, Lee SO. et al. Computed tomography findings in invasive pulmonary aspergillosis in non-neutropenic transplant recipients and neutropenic patients, and their prognostic value. The Journal of infection 2011; 63: 447-456
• 23 Milito MA, Kontoyiannis DP, Lewis RE. et al. Influence of host immunosuppression on CT findings in invasive pulmonary aspergillosis. Medical mycology 2010; 48: 817-823
• 24 Marom EM, Kontoyiannis DP. Imaging studies for diagnosing invasive fungal pneumonia in immunocompromised patients. Current opinion in infectious diseases 2011; 24: 309-314
• 25 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: 611-614
• 26 Bruno C, Minniti S, Vassanelli A. et al. Comparison of CT features of Aspergillus and bacterial pneumonia in severely neutropenic patients. Journal of thoracic imaging 2007; 22: 160-165
• 27 Kami M, Kishi Y, Hamaki T. et al. The value of the chest computed tomography halo sign in the diagnosis of invasive pulmonary aspergillosis. An autopsy-based retrospective study of 48 patients. Mycoses 2002; 45: 287-294
• 28 Caillot D, Couaillier JF, Bernard A. et al. Increasing volume and changing characteristics of invasive pulmonary aspergillosis on sequential thoracic computed tomography scans in patients with neutropenia. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 2001; 19: 253-259
• 29 Horger M, Einsele H, Schumacher U. et al. Invasive pulmonary aspergillosis: frequency and meaning of the “hypodense sign” on unenhanced CT. The British journal of radiology 2005; 78: 697-703
• 30 Won HJ, Lee KS, Cheon JE. et al. Invasive pulmonary aspergillosis: prediction at thin-section CT in patients with neutropenia--a prospective study. Radiology 1998; 208: 777-782
• 31 Greene RE, Schlamm HT, Oestmann JW. et al. Imaging findings in acute invasive pulmonary aspergillosis: clinical significance of the halo sign. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America 2007; 44: 373-379
• 32 Marchiori E, Zanetti G, Hochhegger B. et al. Reversed halo sign on computed tomography: state-of-the-art review. Lung 2012; 190: 389-394
• 33 Kawel N, Schorer GM, Desbiolles L. et al. Discrimination between invasive pulmonary aspergillosis and pulmonary lymphoma using CT. European journal of radiology 2011; 77: 417-425
• 34 Ostrosky-Zeichner L. Invasive mycoses: diagnostic challenges. The American journal of medicine 2012; 125: S14-S24
• 35 Liss B, Vehreschild JJ, Bangard C. et al. Our 2015 approach to invasive pulmonary aspergillosis. Mycoses 2015; 58: 375-382
• 36 Franquet T, Müller NL, Giménez A. et al. Spectrum of Pulmonary Aspergillosis: Histologic, Clinical, and Radiologic Findings. RadioGraphics 2001; 21: 825-837
• 37 Verweij PE, van Die L, Donnelly JP. Halo sign and improved outcome. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America 2007; 44: 1666-1667 ; author reply 1667–1668
• 38 Singh N, Suarez JF, Avery R. et al. Risk factors and outcomes in lung transplant recipients with nodular invasive pulmonary aspergillosis. The Journal of infection 2013; 67: 72-78
• 39 Geltner C, Lass-Florl C. Invasive pulmonary Aspergillosis in organ transplants--Focus on lung transplants. Respiratory investigation 2016; 54: 76-84
• 40 Hekimoglu K, Haberal M, Serifoglu I. et al. Diagnostic Analysis of Computed Tomography Patterns in Patients With Invasive Pulmonary Aspergillosis After Solid-Organ Transplantation. Experimental and clinical transplantation: official journal of the Middle East Society for Organ Transplantation 2019; 17: 216-219
• 41 Qin J, Fang Y, Dong Y. et al. Radiological and clinical findings of 25 patients with invasive pulmonary aspergillosis: retrospective analysis of 2150 liver transplantation cases. The British journal of radiology 2012; 85: e429-e435