DOI: 10.1148/rg.226025101
(Radiographics. 2002;22:1507-1510.)
© RSNA, 2002
Best Cases from the AFIP
Invasive Pulmonary Aspergillosis: Radiologic and Pathologic Findings1
Hai H. Kenney, DO,
Geoffrey A. Agrons, MD and
Jung S. Shin, MD
1 From the Departments of Diagnostic Radiology (H.H.K., G.A.A.) and Pathology (J.S.S.), Pennsylvania Hospital, 800 Spruce St, Philadelphia, PA 19107. Received May 21, 2002; revision requested July 8 and received July 31; accepted August 9. Address correspondence to H.H.K. (e-mail: haikim.nj@netzero.net).
Index Terms: Aspergillosis, 60.2056 • Lung, infection, 60.2056
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History
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A 42-year-old man presented with shortness of breath, increasing substernal chest pressure, hemoptysis, and a productive cough. The patient had a history of late-stage acquired immunodeficiency syndrome (AIDS) with a CD4 cell count of less than 5/mm3 and a viral load of 10,500 copies per milliliter, chronic pancreatitis, and human immunodeficiency virus (HIV) enteropathy. The patient also had a history of pulmonary aspergillosis and was receiving itraconazole therapy. During the hospital course, the patient was diagnosed with Staphylococcus aureus pneumonia proved by culture of bronchoalveolar lavage fluid and was placed on mechanical ventilator support. The patient’s respiratory status continued to deteriorate despite treatment with liposomal amphotericin B and multiple antibiotics. The patient died shortly thereafter.
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Imaging Findings
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Posteroanterior radiographs of the chest from August 2000 and March 2001 revealed an enlarging right upper lobe lung mass with eccentric cavitation (Fig 1a, 1c). Contrast material–enhanced CT of the chest showed an irregular 2.5-cm-diameter mass containing an air crescent sign in the anterior segment of the right upper lobe (Fig 1b).
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Figure 1a. (a) Posteroanterior chest radiograph obtained in August 2000 shows a 2.5-cm-diameter cavitary mass in the right upper lobe. (b) Computed tomographic (CT) scan (lung window) shows that the mass is irregular, is located in the anterior segment of the lobe, and contains an air crescent sign (arrow). (c) Posteroanterior chest radiograph obtained 7 months later shows progressive enlargement of the lesion, which contains a dependent soft-tissue mass.
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Figure 1b. (a) Posteroanterior chest radiograph obtained in August 2000 shows a 2.5-cm-diameter cavitary mass in the right upper lobe. (b) Computed tomographic (CT) scan (lung window) shows that the mass is irregular, is located in the anterior segment of the lobe, and contains an air crescent sign (arrow). (c) Posteroanterior chest radiograph obtained 7 months later shows progressive enlargement of the lesion, which contains a dependent soft-tissue mass.
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Figure 1c. (a) Posteroanterior chest radiograph obtained in August 2000 shows a 2.5-cm-diameter cavitary mass in the right upper lobe. (b) Computed tomographic (CT) scan (lung window) shows that the mass is irregular, is located in the anterior segment of the lobe, and contains an air crescent sign (arrow). (c) Posteroanterior chest radiograph obtained 7 months later shows progressive enlargement of the lesion, which contains a dependent soft-tissue mass.
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Pathologic Evaluation
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Gross pathologic evaluation of the autopsy lung specimen revealed a 6 x 5 x 4-cm right upper lobe cavitary lesion filled with necrotic tissue (Fig 2). Microscopic examination of the lesion showed extensive necrosis and numerous fungal hyphae within the cavity wall (Fig 3a). Septate fungal hyphae were identified extending into normal lung parenchyma (Fig 3b). A fumigatus was isolated from a fungal culture of lung tissue.
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Figure 3a. (a) Photomicrograph (original magnification, x100; Gomori methenamine-silver stain) of a section through the right upper lobe shows numerous fungal hyphae lining the cavity wall and extending into the lung parenchyma. (b) Higher-power photomicrograph (original magnification, x400; Gomori methenamine-silver stain) shows invasion of the lung parenchyma by long, thin, septate fungal hyphae that branch at an approximately 45° angle, an appearance characteristic of Aspergillus fumigatus.
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Figure 3b. (a) Photomicrograph (original magnification, x100; Gomori methenamine-silver stain) of a section through the right upper lobe shows numerous fungal hyphae lining the cavity wall and extending into the lung parenchyma. (b) Higher-power photomicrograph (original magnification, x400; Gomori methenamine-silver stain) shows invasion of the lung parenchyma by long, thin, septate fungal hyphae that branch at an approximately 45° angle, an appearance characteristic of Aspergillus fumigatus.
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Discussion
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Pulmonary aspergillosis is a clinical spectrum of lung disease caused by the fungus A fumigatus. The classification of pulmonary aspergillosis includes saprophytic aspergillosis (aspergilloma), allergic bronchopulmonary aspergillosis (ABPA), chronic necrotizing pulmonary aspergillosis (CNPA), and invasive pulmonary aspergillosis (IPA).
Aspergilloma or mycetoma is a saprophytic mass that colonizes a lung cavity due to preexisting disease such as tuberculosis or sarcoidosis. Patients with pulmonary aspergilloma usually present with recurrent hemoptysis (1,2). New pleural thickening adjacent to a preexisting lung cavity may be the earliest radiographic sign of secondary involvement by aspergillosis (2). As colonization progresses, chest radiography and CT typically demonstrate a solid, round, intracavitary soft-tissue mass separated from the thickened wall by an air crescent sign. The diagnosis of aspergilloma is established by radiographic findings and a positive sputum culture or Aspergillus precipitin test (1). The prognosis of patients with aspergilloma depends on the severity of the underlying pulmonary disease rather than the mycetoma itself. Surgical intervention is reserved for high-risk patients, and treatment is aimed at prevention of life-threatening hemoptysis (1).
Allergic bronchopulmonary aspergillosis (ABPA) is usually a complication of asthma or cystic fibrosis. ABPA is caused by an allergic response characterized by type I and type III hypersensitivity reactions to antigens released by A fumigatus (3). The type I hypersensitivity reaction results in peripheral blood eosinophilia, while the type III hypersensitivity reaction causes pulmonary tissue destruction and bronchiectasis (2). Patients with ABPA commonly experience cough, wheezing, fever, malaise, sputum production, and chest pain. The radiographic and CT findings include upper and middle lung consolidation, bronchial wall thickening, and central bronchiectasis. The "gloved-finger" pattern of radiating perihilar opacities results from bronchial impaction by mucus, Aspergillus hyphae, and debris (2). The diagnosis of ABPA is based on a clinical history of asthma, pulmonary consolidation and bronchiectasis at chest radiography, a cutaneous reaction to Aspergillus antigen, peripheral blood eosinophilia, a positive Aspergillus precipitin test, and increased IgE and IgG antibody levels in the blood (3). Patients with ABPA generally respond well to long-term oral corticosteroid treatment, but exacerbations may occur.
Chronic necrotizing pulmonary aspergillosis (CNPA), also termed semi-invasive pulmonary aspergillosis, is an indolent pulmonary infection commonly seen in mildly immunocompromised patients receiving prolonged corticosteroid therapy. Additional risk factors include diabetes mellitus, alcoholism, and chronic lung disease, such as chronic obstructive pulmonary disease, emphysema, or bronchiectasis (4,5). The slowly progressive disease manifests clinically as chronic cough, fever, generalized fatigue, and weight loss. The most common radiographic and CT findings in patients with CNPA are progressive upper lobe cavitary consolidation, destruction of lung parenchyma, and pleural thickening. Definitive diagnosis requires lung biopsy for demonstration of Aspergillus species (4). Although there are various treatment regimens for CNPA, the most widely used therapeutic agent is intravenous amphotericin B. Intracavitary amphotericin B administration is also a treatment option. However, clinical benefits have been demonstrated in a limited number of cases (6). Treatment outcomes for patients with CNPA vary with the severity of the chronic underlying illness.
Invasive pulmonary aspergillosis (IPA) is characterized by hyphal invasion and destruction of normal lung tissue. IPA affects patients with prolonged neutropenia due to AIDS or with hematologic malignancies and those who have undergone organ transplantation. IPA usually occurs in patients with advanced AIDS and a CD4 cell count of less than 50/mm3 (7,8). Clinical manifestations of IPA include cough, chest pain, and hemoptysis.
Owing to the high mortality rate associated with IPA in the immunocompromised patient, early diagnosis and aggressive treatment are essential. Radiographic evaluation, although nonspecific, may reveal poorly defined pulmonary nodules or air-space consolidation early in the disease process. Thick-walled cavitary lesions, as demonstrated in our case (Fig 1c), represent a late finding. At high-resolution CT, the term halo sign is applied to a masslike lung consolidation or nodule surrounded by ground-glass attenuation, corresponding to hemorrhagic necrosis (2,9). Bronchoalveolar lavage often suggests the diagnosis but has a low diagnostic yield. Similarly, sputum cultures are positive in only 12% of HIV-infected patients with IPA (7). Definitive diagnosis often requires lung biopsy, but patients may be too ill to undergo this invasive procedure. In our case, the diagnosis of IPA was confirmed histologically by invasion of normal lung tissue and pulmonary parenchymal destruction by A fumigatus. Amphotericin B remains the treatment of choice. However, the efficacy of antifungal therapy combined with 5-flucytosine, itraconazole, and rifampin, as well as new antifungal drugs including voriconazole, echinocandins, and pneumocandins, is under investigation (10,11). Despite early aggressive antifungal treatment, the prognosis of HIV-positive patients with IPA is poor.
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Footnotes
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Editor’s Note.—Everyone who has taken the course in radiologic pathology at the Armed Forces Institute of Pathology (AFIP) remembers bringing two beautifully illustrated cases for accession to the Institute. In recent years, the staff of the Department of Radiologic Pathology has judged the "best cases" by organ system, and recognition is given to the winners on the last day of the class. With each issue of RadioGraphics, one or more of these cases are published, written by the winning resident. Radiologic-pathologic correlation is emphasized, and the causes of the imaging signs of various diseases are illustrated.
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References
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- Tomee JFC, van der Werf TS. Pulmonary aspergillosis. Neth J Med 2001; 59:244-258.[CrossRef][Medline]
- Franquet T, Muller NL, Gimenez A, Guembe P, de la Torre J, Bague S. Spectrum of pulmonary aspergillosis: histologic, clinical, and radiologic findings. RadioGraphics 2001; 21:825-837.[Abstract/Free Full Text]
- Vlahakis NE, Aksamit TR. Diagnosis and treatment of allergic bronchopulmonary aspergillosis. Mayo Clin Proc 2001; 76:930-938.[Medline]
- Kato T, Usami I, Morita H, et al. Chronic necrotizing pulmonary aspergillosis in pneumoconiosis: clinical and radiologic findings in 10 patients. Chest 2002; 121:118-127.[Abstract/Free Full Text]
- Dupont B, Richardson M, Verweij PE, Meiss JFGM. Invasive aspergillosis. Med Mycol 2000; 38:215-224.
- Saraceno J, Phelps DT, Ferro TJ, Futerfas R, Schwartz DB. Chronic necrotizing pulmonary aspergillosis: approach to management. Chest 1997; 112:541-548.[Abstract/Free Full Text]
- Mylonakis E, Barlam TF, Flanigan T, Rich JD. Pulmonary aspergillosis and invasive disease in AIDS: review of 342 cases. Chest 1998; 114:251-262.[Abstract/Free Full Text]
- Shah RM, Kaji AV, Ostrum BJ, Friedman AC. Interpretation of chest radiographs in AIDS patients: usefulness of CD4 lymphocyte counts. RadioGraphics 1997; 17:47-58.[Abstract]
- Abramson S. The air crescent sign. Radiology 2001; 218:230-232.[Free Full Text]
- Patterson TF, Kirkpatrick WR, White M, et al. Invasive aspergillosis: disease spectrum, treatment practices, and outcomes. Medicine 2000; 79:250-260.[CrossRef][Medline]
- Paterson DL, Singh N. Invasive aspergillosis in transplant recipients. Medicine 1999; 78:123-138.[CrossRef][Medline]
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History
Imaging Findings
