Pulmonary Aspergillosis: Radiographic findings from immunosuppressed patient to hyperreactive host.

Transcription

1 Pulmonary Aspergillosis: Radiographic findings from immunosuppressed patient to hyperreactive host. Poster No.: C-1442 Congress: ECR 2013 Type: Educational Exhibit Authors: C. P. Fernandez Ruiz, S. Isarria, M. L. Domingo, D. H. Jiménez, R. Revert Espí, Y. Fernandez Nuñez; Valencia/ES Keywords: Inflammation, Infection, Cavitation, Education, Conventional radiography, CT, Thorax, Lung DOI: /ecr2013/C-1442 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 36

2 Learning objectives To review the wide spectrum of the imaging and clinical features of Pulmonary aspergilosis from saprophytic form to invasive types and to provide key points for differential diagnosis. Page 2 of 36

3 Background There are approximately 200 species of Aspergillus, isolated from the soil, plant debris and the indoor environment, but only a few are known to be pathogenic for humans. The most frequent pathogenic specie is A fumigatus Fig. 1 on page 4. Aspergillus spp are ubiquitous fungi acquired by inhalation of airborne spores that have a small diameter enough (2 to 3 mm) to reach the lung alveoli. Environmental surveys indicate that humans inhale at least several hundred A. fumigatus spores per day. Inhalation of spores by immunocompetent individuals rarely has any adverse effect, because are eliminated ef#ciently by innate immune mechanisms. In the past, A. fumigatus was viewed as a weak pathogen, but it may cause a continuous spectrum of histopathologic, clinical and radiologic manifestations according the number, virulence of the organisms and the patient's immune response Fig. 2 on page 4. The spectrum of this disease begins with two non-invasive pulmonary diseases, Allergic Bronchopulmonary Aspergillosis (ABPA) and the Aspergilloma as a saprophytic form. Following we can find semi-invasive forms as chronic necrotizing aspergillosis (CAN) and the airway-invasive aspergillosis (AIA). This wide spectrum ends with Angio-invasive pulmonary aspergillosis (IA), a major cause of mortality in severely immunocompromised patients. Page 3 of 36

4 Images for this section: Fig. 1: Typical microscopic features of typical A. fumigatus demonstrates sporulating structures. Page 4 of 36

5 Fig. 2: The spectrum of clinical and radiological manifestations relative to degree of immune-suppression. The risk of invasive disease increases concomitant with the degree of immune suppression. Page 5 of 36

6 Imaging findings OR Procedure details The poster reviews the clinical and imaging features of the main categories of Pulmonary Aspergillosis, emphasizing key points for their diagnostic, without forget that findings can overlap between them. 1. ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS (ABPA). ABPA is a hypersensitivity reaction to Aspergillus antigens seen in patients with longstanding asthma or cystic fibrosis. This complex hypersensitivity reaction (type I and III) to Aspergillus organisms that proliferate in the airway lumen, results in a constant supply of antigen with excessive mucus production and abnormal ciliary function. Fungal hyphae were commonly seen in mucoid plugs without evidence of tissue invasion. Findings as the mucoid impaction, bronchial wall damage and bronchiectasis are typical of this disease with involving the segmental and subsegmental bronchi. Clinical presentation: Almost all patients have clinical asthma, and patients usually present with episodic wheezing, expectoration of sputum containing brown plugs, pleuritic chest pain, and fever. Episodes of recurrent pneumonias in patients with asthma suggest this disease. Imaging: During acute exacerbations, Chest radiograph shows migratory tubular areas of opacification due to mucoid impaction of the airways, these appears as bronchial opacities that irradiated from the hilum with rounded distal margin called " finger-inglove" sign (Fig. 3 on page 14). in the upper lobe and central in location. The "ring sign" and "tram lines" by thickened and inflamed bronchi may be seen too. Central bronchiectasis (Fig. 4 on page 14) and pulmonary fibrosis may develop at later stages. CT findings include lobar or segmental atelectasis and bronchiectasis with mucoid impaction involving predominantly the segmental and subsegmental bronchi of the upper lobes (Fig. 5 on page 15) Key points: Page 6 of 36

7 Central bronchiectasis with mucoid plugs in patient with asthma. The plugs may have high attenuation or demonstrates frank calcification at CT. Treatment: The mainstay of therapy for ABPA is oral corticosteroids to suppress the immunologic response to Aspergillus antigens and the secondary inflammatory reaction. The duration of therapy should be individualized according to the patient's clinical condition but most of them require prolonged therapy to control their symptoms and minimize relapses. Nowadays, Antifungal agents don't have demonstrated better results than corticosteroids. 2. ASPERGILLOMA (SAPROPHYTIC ASPERGILLOSIS ) The aspergilloma (fungus ball) is a mass composed of fungal hyphae, inflammatory cells, fibrin, mucus and tissue debris that develops in a pre-existing cavity in the lung, without invade the surrounding lung parenchyma or blood vessels. Many cavitary lung diseases are complicated by aspergilloma, including tuberculosis, the most common condition, sarcoidosis, bronchiectasis, bronchial cysts,bulla, pneumatoceles, ankylosing spondylitis, neoplasm, and pulmonary infarction. Clinical presentation: Most patients with aspergilloma are asymptomatic. When symptoms are present, they will experience mild haemoptysis, but severe and lifethreatening haemoptysis may occur in patients with underlying tuberculosis. Less commonly, patients may develop cough and dyspnea but probably related to the underlying lung disease. Imaging: Chest X-Ray shows an spherical and solid, intracavitary mass (Fig. 6 on page 16), usually surrounded by a radiolucent crescent. CT scan shows round mass of soft-tissue density opacity within a lung cavity with an airspace of variable size and shape, resulting in the "Monod sign" (Fig. 7 on page 17). This radiological sign may seen in other different conditions as hydatid cyst, Rasmussen aneurysm in a tuberculous cavity, lung abscess, bronchogenic carcinoma, hematoma and Wegener's granulomatosis. Without forgetting that Aspergilloma may coexist with any of the above mentioned conditions. Page 7 of 36

8 Key points: A change in the position of the fungus ball after moving the patient (Fig. 8 on page 18 ), demonstrating that this mass is mobile because does not usually invade the surrounding lung parenchyma. The mass is usually separated from the wall of the cavity by an variable airspace variable, known the "Monod sign" (Fig. 7 on page 17). An early sign of aspergilloma formation in a cavity is pleural thickening which often antedates the radiographic features of an obvious intracavitary fungus ball (Fig. 9 on page 19 ). An increase in wall thickness of the lateral aspect of a fibrotic cavity, reflecting a combination of pleural and cavity wall thickening, may be a helpful sign of radiographically cryptic aspergilloma. Treatment: In the majority of the cases, Aspergilloma remains stable and 10% of cases may resolve spontaneously without treatment. Surgical resection of the cavity and removal of the fungus ball is usually indicated in patients with recurrent haemoptysis, if their pulmonary function is sufficient to allow surgery or bronchial artery embolization in patients with poor lung function. 3. SEMI-INVASIVE ASPERGILLOSIS. Chronic Necrotizing Aspergillosis or Semi-invasive aspergillosis is an indolent, destructive process of the lung due to local invasion by Aspergillus species, with tissue necrosis and granulomatous inflammation. The histological spectrum includes a necrotizing granulomatous pneumonia around a central zone of infarct-like necrosis of parenchyma and a granulomatous bronchiectatic cavity with a central fungus ball and subtle tongues of necrosis extending through the fibrous wall of the cavity. There is not vascular invasion or dissemination to other organs at this entity. Clinical presentation: Page 8 of 36

9 Patients frequently complain of constitutional symptoms with a slowly progressive course over weeks to months, fever, weight loss, malaise, chronic productive cough and haemoptysis, which vary from mild to severe. These are middle-aged and elderly patients with mild immunosuppression, including those with diabetes mellitus, poor nutrition, corticosteroid therapy, and those underlying lung diseases like COPD, inactive tuberculosis, previous lung resection, radiation therapy and pneumoconiosis. Imaging The chest radiograph usually shows unilateral or bilateral areas of consolidation, with or without cavitation in the upper lobes or the superior segments of the lower lobes (Fig. 10 on page 20 ). Adjacent pleural thickening is a characteristic finding and maybe an early indication of a locally invasive process. CT findings consist of segmental areas of consolidation in the upper lung lobes, with cavities of thick wall and satellite foci of increased opacity (Fig. 11 on page 21). Adjacent pleural thickening, which may progress to form a broncho-pleural fistula, it is considered an early indication of a locally invasive process. These radiological findings tend to be progressive over weeks to months. An unusual subtype is the necrotizing bronchitis by Aspergillus, that can appear as a endobronchial mass, circumferential bronchial wall thickening, obstructive pneumonitis with collapse or a hilar mass. Key points : Formation of new cavity or expansion of cavity size over time (weeks to months) inside pulmonary consolidation (Fig. 12 on page 22) in a mild immunosuppressed patient, even though these findings could be viewed in some other diseases. Treatment: Antifungal medications are indicated once the diagnosis is made. Surgical resection is generally reserved for healthy young patients with focal disease and good pulmonary reserves or patients not tolerating antifungal therapy. 4. AIRWAY-INVASIVE ASPERGILLOSIS (AIA) Page 9 of 36

10 Airway-invasive aspergillosis is characterized by the presence of Aspergillus organisms deep to basement membrane of bronchi or bronchioles, usually with a neutrophil reaction and presence of hyphae in the involved airway. Surrounding the airway is often found a variably sized zone of hemorrhage and/or organizing pneumonia. Given the anatomic proximity of the bronchi to pulmonary arteries, it is not surprising that this entity co-exists with invasive form in the same patient, and it is not always possible to distinguish them. This entity including tracheobronchitis,bronchitis, bronchiolitis, bronchopneumonia or lobar pneumonia, without evidence of vascular invasion. A rare type of AIA is the Obstructing Bronchopulmonary Aspergillosis, a noninvasive form of aspergillosis that is characterized by the massive intraluminal overgrowth of Aspergillus in patients with AIDS. Clinical presentation: Most patients have fever, cough, and progressive dyspnea. It is common in immunocompromised neutropenic patients and in patients with AIDS. Imaging The radiographic findings of airway-invasive aspergillosis are nonspecific, ranging from normal in tracheobronchitis and ill-defined nodules in bronchiolitis, to patchy areas of consolidation of lower lobe predominance in cases of bronchopneumonia Thoracic CTshows centrilobular nodules (<5 mmin diameter) that are connected to linear, branching opacities that have more than one contiguous branching site, finding known as tree in bud, suggestive of Bronchiolitis (Fig. 13 on page 23); ground-glass attenuation and patchy areas of consolidation up to 5 cm in diameter in cases of bronchopneumonia by Aspergillus. Centrilobular nodules of increased opacity similar to those seen in Aspergillus bronchiolitis have been described in a number of infectious conditions as endobronchial spread of pulmonary tuberculosis, Mycobacterium avium-intracellulare, viral and mycoplasma pneumonia. Obstructing Bronchopulmonary Aspergillosis mimics at allergic bronchopulmonary aspergillosis with bilateral bronchial and bronchiolar dilatation, large mucoid impactions (mainly in the lower lobes), and diffuse lower lobe consolidation caused by postobstructive atelectasis (Fig. 14 on page 24, Fig. 15 on page 25 ). Key points: Page 10 of 36

11 Centrilobular micronodules with "tree in bud" or consolidation or ground-glass attenuation of peribronchial or peribronchiolar localization in immunocompromised patients with symptoms progressive and without response to antibiotics. Radiologic manifestations are indistinguishable from those caused by other microorganisms. Treatment: Patients are treated as CNA with systemic antifungals (itraconazole orally or intravenous amphotericin B), surgery and in a few cases intracavity amphotericin-b. 5. ANGIOINVASIVE ASPERGILLOSIS (IA). It's the most aggressive form of aspergillosis, with a mortality rate that may exceed 50%. It occurs when the hyphae invade bronchial wall and subsequently the accompanying arterioles, with consequent thrombosis and the formation of necrotic hemorrhagic nodules or subpleural wedge-shaped hemorrhagic infarcts. IA is seen almost exclusively in severely immunocompromised. Neutropenia is the most important risk factor, following by prolonged Corticosteroid therapy, transplantation, hematologic malignancy, Cytotoxic therapy and AIDS. Clinical presentation: Patients present inespecific symptoms, that suggest bronchopneumonia as fever unresponsive to antibiotics, cough, sputum production, and dyspnea. In addition, pleuritic chest pain due to vascular invasion, leading to small pulmonary infarcts. IA is one of the most common causes of haemoptysis in neutropenic patients, this symptom is associated with cavitation that occurs with neutrophil recovery. Aspergillus may disseminate to another organs, most commonly to the brain (seizures, ring-enhancing lesions, cerebral infarctions, intracranial haemorrhage, meningitis and epidural abscess), skin, kidneys, heart, esophagus and liver. Imaging The chest radiograph may appear normal up to 25% of patients. Radiographic abnormalities include single or multiple nodular infiltrates; segmental or subsegmental consolidation; diffuse ground-glass pattern (often progressing to consolidation) and cavitation (air-crescent sign) (Fig. 16 on page 26 ); pleural effusions are uncommon. Page 11 of 36

12 The routine use of chest CT scans in patients with suspected IA has been associated with better outcomes, probably due to earlier diagnosis. Chest CT scan may shows early in the course of infection (usually in the first week), multiple nodules surrounded by areas of ground-glass attenuation known as halo sign and areas of segmental and non-segmental consolidation, which are often bilateral, with or without a halo (Fig. 17 on page 27). "The halo sign" represents haemorrhage around a pulmonary nodule and is highly suggestive of angioinvasive aspergillosis. This sign was regarded pathognomonic some years ago, however it may be present in others fungal and viral infections, Wegener granulomatosis, Kaposi sarcoma, hemorrhagic metastases, bronchiolitis obliterans organizing pneumonia and bronchoalveolar carcinoma. Another finding are wedge-shaped areas of consolidation with a broad base abutting a peripheral pleural surface by hemorrhagic infarcts. The cavitation and "air crescent sign" are viewed when area of necrotic tissue is reabsorbed from the periphery, which causing retraction of the infarct from viable lung parenchyma and leaves a space of air surrounding, this is usually seen during convalescence, 2 to 3 weeks after initiation of treatment and coincident with resolution of the Neutropenia (Fig. 18 on page 28, Fig. 19 on page 29). This air-space doesn t change with position of patient and it s different to monod sign of aspergilloma. Key Points: Both signs: Halo and air crescent are relatively specific for IA in immunocompromised patients (Fig. 20 on page 30, Fig. 21 on page 31), but the halo sign is seen much earlier, when We see it, We should suspect IA. The air crescent sign usually correlates with recovery from neutropenia. Treatment The treatment of IA is difficult and the mortality rate remains high despite recent advances in therapy. Empiric therapy should be started as soon as there is clinical suspicion of IA. The most widely used drug in the treatment is amphotericin B. Surgical resection should be considered always in cases of massive hemoptysis and the resection of residual localized pulmonary lesions in patients with continuing immunosuppression or those who are expected to have further immunosuppressive therapy in the future. GRADING AND OVERLAP Page 12 of 36

13 BuckIngham et al. described multiple studies that demonstrated that the forms of Pulmonary Aspergillus can change in any given patient with time and could overlap each other. This linkage may be viewed in longstanding ABPA, the bronchi may show marked bronchiectatic change and aspergillomas may form within them (Fig. 22 on page 32, Fig. 23 on page 33) ; some patients with ABPA could developing chronic airway invasive aspergillosis with the high degree of pre-existing bronchial wall damage and systemic immune factors as the use of high-dose steroids. Although aspergillomas are thought of as an indolent saprophytic growth, there are cases of subsequent invasive aspergillosis well described. Page 13 of 36

14 Images for this section: Fig. 3: Chest X ray in a 58-year-old woman with ABPA, with overinflated lungs by asthma and dilatation with bronchial wall thickening compatible with bronchiectasis of central localization and in the upper lobes. Note "finger in glove" appearance (long arrow) corresponding to mucoid impaction of some proximal bronchi. Page 14 of 36

15 Fig. 4: High-resolution CT in the Coronal (a) and axial (b,c) planes of the previous patient with ABPA, that shows cylindrical and varicosae bronchiectasis (arrow) of central location and bilateral and multiple tubular areas of increased attenuation "finger in glove" (arrowhead) by mucoid impaction. Page 15 of 36

16 Fig. 5: High-resolution CT in the coronal (a,b) and axial (c,d) planes of 37-year-old woman with asthma and ABPA, that shows typical proximal cilindrical bronchiectasis with areas of mucoid impaction (arrow). Page 16 of 36

17 Fig. 6: The classical mycetoma. Chest X ray shows large rounded mass at the left apex with an air-crescent radiolucency (long arrow) and associated lateral pleural thickening (short arrow), in patient with COPD and chronic changes in both upper lobes by tuberculosis. Page 17 of 36

18 Fig. 7: Chest CT (lung window) in axial (a,b) and coronal (c) planes of the same patient shows cavities bilaterally in the upper lobes containing fungus balls (long arrow) and extensive scarring in the upper lobes. A large aspergilloma is seen in the left upper lobe, with a characteristic air crescent sign ( short arrow) between the aspergilloma and the cavity wall. Note the marked pleural thickening surrounding the cavity containing the aspergilloma (curve arrow). Page 18 of 36

19 Fig. 8: Thoracic CT shows mobile aspergilloma within a pulmonary cystic cavity obtained with the patient supine (a) and prone (b) show a change in the position of the fungus ball. Page 19 of 36

20 Fig. 9: Thoracic CT (lung window) in axial plane demonstrates multiple fungus balls filling a pulmonary cavity in the left upper lobe with air crescent sign (arrow). Page 20 of 36

21 Fig. 10: Chest X-Ray in a 81-year-old man with long standing corticosteroid therapy and Semi-invasive Aspergillosis. Overinflated lungs by COPD and a large area of air-space consolidation in left upper lobe, heterogeneus with cavitation and thickened edges of high density. Page 21 of 36

22 Fig. 11: Thoracic CT in axial (a,b) and coronal (c,d) planes of previous patient shows in left upper lobe, a rounded area of consolidation (arrow) that associate cavitation irregular of coarse wall and adjacent pleural thickening (short arrow), findings suggest of Chronic Necrotizing Aspergillosis. Page 22 of 36

23 Fig. 12: Radiographic features of chronic necrotizing aspergillosis in a patient of 66years-old with coexisting alveolar proteinosis.chest X-ray (a) and Chest CT (lung window) in coronal (b) and axial (c,d) planes An round air-space consolidation in left lower lobe with minimal pleural thickening (arrow), without cavitation. Furthermore some small foci of increased opacity in right lower lobe (*) representing an additional site of disease. Page 23 of 36

24 Fig. 13: Acute airway-invasive aspergillosis. High-resolution CT demonstrates multiple centrilobular nodules (long arrow) with areas of branching linear known as "tree-inbud" (short arrow), in a oncologic patient with bronchiolitis by aspergillus Page 24 of 36

25 Fig. 14: Necrotizing bronchial aspergillosis in a 40-year-old man without known immunosuppression. Chest X-ray shows a right hilum enlarged and an area of increased density (arrow) in the posterior segment of right lower lobe. Page 25 of 36

26 Fig. 15: Chest CT scan in axial planes with lung (a,c) and mediastium (b y d) window of previous patient demonstrates a solid mass (long arrow) with lobulated margin and areas of necrosis that obstruct the intermediate bronchus (short arrow) with associated segmental atelectasis. Mediastinal adenopathies are present. This findings suggested initially lung cancer. Page 26 of 36

27 Fig. 16: Angioinvasive aspergillosis in a 50-year-old man with neutropenia. Portable Chest X-ray shows an air-space consolidation with in broad contact with oblique fissure in right upper lobe (arrow). Page 27 of 36

28 Fig. 17: CT scan of the anterior patient in coronal (a,b) and axial (c,d) planes shows a consolidation (large arrow) in right upper lobe abutting the pleura and demarcated by an oblique fissure, surrounding by "halo sign" (short arrow). Page 28 of 36

29 Fig. 18: Angioinvasive Aspergilosis in a 63-year-old man with oropharyngeal cancer in treatment with chemotherapy in recovering phase. Chest X-Ray that demonstrates an air-space consolidation (arrow) in right upper lobe with small area of cavitation inside. Page 29 of 36

30 Fig. 19: CT scan of previous patient in axial (a,b) and coronal (c,d) planes shows spherical air-space consolidation (arrow) in right upper lobe with associated cavitation and a surrounding ground-glass attenuation called "halo sign" (arrowhead), typical finding that representing adjacent hemorrhage because hyphal invasion of blood vessels Page 30 of 36

31 Fig. 20: Angioinvasive aspergillosis in a 60-year-old man with idiopathic myelofibrosis. Portable Chest X-ray shows an air-space consolidation with a cavitation in right lower lobe (arrow). Page 31 of 36

32 Fig. 21: CT scan of previous patient in axial plane (a,b) shows air-space consolidation (arrow) in lower right lobe with associated cavitation and a surrounding ground-glass attenuation called "halo sign" (arrowhead). Page 32 of 36

33 Fig. 22: Chest x-ray in a 54-year-old woman with multiple cystic and tubular images (arrowhead) and loss of volume in both upper lobes. In right lower lobe, there are various "Gloved-finger" images (arrow) corresponding to bronchiectasis with mucoid impaction and an air-space consolidation in the right upper lobe with associated cavitation (curve arrow). Page 33 of 36

34 Fig. 23: HRCT in coronal (a,b) and axial (c,d) planes of the previous patient demonstrates co-existing aspergilloma (arrow) in a patient with longstanding ABPA. Fungus ball is in the left upper lobe and demostrates thickening pleural associated. Multiple central bronchiectasis, some of them with mucoid impaction (curve arrow). Page 34 of 36

35 Conclusion Pulmonary Aspergillosis is a disease with a wide radiologic spectrum according to the host s inmunosuppression. Knowing the typical radiographic signs of different forms of aspergillosis in a appropriate clinical setting could help us to reach diagnosis. Page 35 of 36

36 References Franquet, T et al. Spectrum of Pulmonary Aspergillosis: Histologic, Clinical, and Radiologic Findings. RadioGraphics 2001; 21: Latge, J. Aspergillus fumigatus and Aspergillosis. Clin. Microbiol. Rev. 1999, 12(2):310. Buckingham,S, Hansell, d. Aspergillus in the lung: diverse and coincident forms. Eur Radiol 2003; 13: Soubani, A. The Clinical Spectrum of Pulmonary Aspergillosis. CHEST 2002; 121: Zmeili O, Soubani A. Pulmonary aspergillosis: a clinical update Q J Med 2007; 100: Logan PM, Mu ller NL. CT manifestations of pulmonary aspergillosis. Crit Rev Diagn Imaging 1996; 37:1-37. Gefter WB. The spectrum of pulmonary aspergillosis. J Thorac Imaging 1992; 7: Miller WT Jr, Sais GJ, Frank I, Gefter WB, Aronchick JM, Miller WT. Pulmonary aspergillosis in patients with AIDS: clinical and radiographic correlations. Chest 1994; 105: Page 36 of 36