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Semi-invasive Aspergillosis With Chest Wall and Spinal Involvement: A Case Report and Discussion

Vagal, Achala S. MD*; Starnes, Sandra MD; Bakkar, Rania MD; Meyer, Cris A. MD*

Infectious Diseases in Clinical Practice: November 2006 - Volume 14 - Issue 6 - p 369-372
doi: 10.1097/IPC.0b013e31802bd078
Radiology in ID

Although aspergillus infection is seen relatively frequently in immunosuppressed patients, chest wall and spinal invasion with bony destruction is rare. Aspergillus infection can cause a wide spectrum of lung disease, ranging from simple colonization to life-threatening invasive aspergillosis, depending on the immune status of the host or preexisting lung disease. We present a case report of a patient with history of treated lung carcinoma who demonstrated the gradual progression of an aspergilloma to a semi-invasive form with direct involvement of the chest wall and mediastinum, causing frank destruction of the ribs and thoracic spine. The spectrum of pulmonary aspergillosis and differential diagnosis of pulmonary disease secondarily invading the chest wall has been discussed.

*Department of Radiology, †Division of Thoracic Surgery and ‡Department of Pathology, University of Cincinnati College of Medicine and Cincinnati VA Medical Center, Cincinnati, OH.

Address correspondence and reprint requests to Achala Vagal, MD, University of Cincinnati Medical Center, 234 Goodman Street ML 0761, Cincinnati, OH 45267-0761. E-mail:

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This is a case report of a 65-year-old man who originally presented in 1998 with weight loss. A chest computed tomography (CT) at that time demonstrated a right paratracheal mass for which he underwent a right thoracotomy with biopsy of the level 4R mediastinal lymph nodes. No intrapulmonary mass was found at the time of exploration. Pathology revealed nonsmall cell lung cancer. He was treated as a stage IIIA (TXN2MO) nonsmall cell lung cancer with definitive chemotherapy (carboplatin, taxol, and amifostine) and radiation (6100 cGy).

He remained asymptomatic with no evidence of recurrent disease until November 2004 when he presented with hemoptysis. Chest CT demonstrated radiation changes in the right upper lobe along with apical soft tissue containing irregular air spaces (Fig. 1A). Cultures from bronchoscopy revealed aspergillus, and a CT-guided biopsy revealed no evidence of recurrent malignancy. The patient was treated with itraconazole for 3 months. Follow-up CT in January 2005 demonstrated interval growth of cavitary lesion in the right apex with development of a more discrete mycetoma (Fig. 1B). In October 2005, his chest CT demonstrated increasing soft tissue with new mixed lytic and sclerotic lesions of the T3 through T5 thoracic vertebrae with involvement of the adjacent right posterior ribs (Fig. 1C). At that time, he was symptomatic requiring narcotics for significant back pain. A positron emission tomography scan demonstrated uptake in the right apex of the lung, posterior mediastinum, and T1 to T4 vertebral bodies. The CT and magnetic resonance imaging of the thoracic spine revealed right paraspinal soft tissue enveloping T1 through T6 vertebrae with extensive osseous destruction and vertebral body collapse (Fig. 1D). In addition, there was evidence of concentric epidural soft tissue with moderate cord compression at these levels (Fig. 1E). The CT-guided percutaneous biopsy of the involved vertebral bodies was performed twice and nondiagnostic both times.



Because of the suspicion of recurrent malignancy despite negative percutaneous biopsies, he underwent left video-assisted thoracoscopy (VATS) in March 2006. A left-sided approach was chosen because of the previous thoracotomy and radiation to the right chest, which would make a right-sided approach unsafe. At the time of surgery, the mediastinal pleura was opened over the involved vertebral bodies. Biopsies were taken from multiple levels of the involved vertebrae. Pathology revealed no evidence of malignancy. Cultures from the bone grew Aspergillus fumigatus.

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Semi-invasive aspergillosis with chest wall and spinal involvement.

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Aspergillus species are ubiquitous molds found in organic matter. Although more than 100 species have been identified, most human illness is caused by A. fumigatus and Aspergillus niger and, less frequently, by Aspergillus flavus and Aspergillus clavatus. The transmission of fungal spores to the human host is via inhalation. A wide spectrum of lung disease is reported based on the immune status of the host or the presence of preexisting lung disease. This ranges from simple colonization (mycetoma) to chronic necrotizing aspergillus in mildly immunocompromised patients to life-threatening invasive aspergillosis in severely neutropenic patients. In addition, allergic bronchopulmonary aspergillosis (ABPA) can result from colonization of the airways with development of delayed type hypersensitivity reaction. Finally, invasive tracheobronchial aspergillosis has been described in patients with acquired immunodeficiency syndrome. Although aspergillus infection is common in severely immunosuppressed patients, tissue invasion and extension across tissue planes in an immunocompetent patient is rare. We describe a case of aspergillus infection with chest wall and spinal invasion as a late complication of radiation therapy for lung cancer.

The differential diagnosis of pulmonary disease with secondary chest wall invasion includes the 2 main categories of malignancy and infections. Lung infections that secondarily involve the chest wall include pathogens such as actinomycetes, nocardia, aspergillus, Mycobacterium tuberculosis as well as pyogenic organisms, such as staphylococcus and klebsiella species. Radiological findings of chest wall infections include presence of chest wall or extra pleural mass, pleural thickening, pleural effusions, and bony involvement including rib or vertebral erosions or sclerosis. Proliferation of the extra pleural fat is a finding associated with indolent infectious processes. The most common neoplastic processes to involve the chest wall and lung parenchyma include bronchogenic carcinoma, breast cancer, and lymphoma.

Thoracic actinomycosis is a chronic suppurative pulmonary or endobronchial infection caused by actinomyces species, most frequently Actinomyces israelii, a gram-positive anaerobic saprophytic organism in the oral cavity. Actinomycosis produces proteolytic enzymes, which do not respect tissue planes.1 It is also well known for its tendency to secondarily involve the chest wall from a pulmonary process. When a lesion violates typical anatomical boundaries, crossing tissue and fascial planes by extending across a fissure or into the chest wall, the diagnosis of actinomycosis should be considered. According to Cheon-Cheon et al,2 chronic segmental air-space consolidations that contain low-attenuation areas with peripheral enhancement and adjacent pleural thickening are typical CT findings of pulmonary actinomycosis (Fig. 2). Wavy periostitis of the ribs is also considered typical of actinomycosis.3



Tuberculous abscesses of the chest wall, although uncommon, may be encountered in endemic regions. Tuberculous abscesses of the chest wall can involve the sternum, costochondral junctions, rib shafts, costovertebral joints, and the vertebrae. They are most frequently found at the margins of the sternum and along the rib shafts.4 Tuberculosis (TB) is second only to metastasis as a cause of rib destruction and is the most commonly encountered inflammatory lesion of the ribs.5 The spontaneous discharge of a tuberculous empyema through the parietal pleura, into the chest wall, to form a subcutaneous abscess with eventual rupture through the skin is termed an empyema necessitans.6

Nocardia asteroides is a filamentous, gram-positive, and weakly acid-fast pyogenic bacillus that is closely related to actinomyces and rhodococcus species.7 In the lung, nocardiosis typically produces single or multiple abscesses. Pleural involvement, usually fibrous thickening or empyema, is frequent. Chest wall extension may occur.

Pulmonary aspergillosis can be subdivided into 4 categories: (a) saprophytic aspergillosis (aspergilloma), (b) hypersensitivity reaction (ABPA), (c) semi-invasive (chronic necrotizing) aspergillosis, and (d) invasive aspergillosis.8 However, it has been suggested that pulmonary aspergillosis be considered as a spectrum because the described categories may overlap in individual patients.9 In the described case, the process initially had the appearance of a mycetoma. Subsequent development of pleural thickening is more typical of semi-invasive or chronic necrotizing aspergillus. At the time of surgery, involvement of the chest wall and spine implies a progressively invasive process.

Aspergillomas consist of intraluminal masses of hyphae, blood clot, and cellular debris that typically colonize preexisting cavities. The most common underlying causes are TB and sarcoidosis. New pleural thickening adjacent to a preexisting lung cavity may be the earliest radiographic sign of secondary involvement by aspergillosis.10 The classic radiographic or CT appearance of an aspergilloma or a fungal ball is a rounded mass of soft tissue density in a preexisting cavity partially surrounded by crescent of air. The mobility of the fungal ball is critical to the diagnosis and should be demonstrated with use of prone and supine positions to exclude an endocavitary mass (Fig. 3). In other cases, the aspergilloma appears as an irregular sponge work containing air spaces and filling the cavity, obliterating the air crescent. An aspergilloma is usually characterized by aspergillus infection without tissue invasion. Invasion into the adjacent lung parenchyma or chest wall does not occur unless host defense mechanisms are compromised. The condition can then take on a locally destructive form, known as chronic necrotizing or semi-invasive aspergillosis.11 In our case, the patient had had prior radiation therapy, leading to locally devitalized lung as the predisposing breach in host defenses.



Semi-invasive aspergillosis, also known as chronic necrotizing aspergillosis, is characterized at histological analysis by the presence of tissue necrosis and granulomatous inflammation similar to that seen in reactivation TB.12 In patients with semi-invasive pulmonary aspergillosis, abnormalities in the host's defense mechanism are frequently present. Typically, patients have poor nutrition caused by alcoholism, diabetes mellitus, chronic granulomatous disease, or connective tissue disorders. Pulmonary abnormalities such as a fibrotic area of mycobacterium species, chronic obstructive lung disease, previous surgery, radiation therapy, pulmonary infarction, or pneumoconiosis may also lower defense mechanisms. Prior radiation therapy with relative tissue devitalization was the likely breach in host defense mechanism in this case.

This unusual form of pulmonary aspergillosis resembles many chronic pulmonary diseases including TB, actinomycosis, histoplasmosis, and carcinoma.13 Radiographs reveal an indolent consolidation that tends to involve the upper lobes with associated pleural thickening. Upper lobe nodules or a masslike consolidation can also be seen. This upper lobe predominance may be related to the fact that underlying diseased areas of lung promotes this form of infection. The findings are similar to those seen with TB. In chronic obstructive pulmonary disease patients with semi-invasive aspergillosis, a high prevalence of cavitation can be seen.12 The semi-invasive form of aspergillosis is classically indolent and usually progresses over a period of weeks to months to cavitation in about half the cases and mycetoma formation occurs in up to 50%. In addition, extension into the chest wall and mediastinum may be seen, as was seen in this case.

Invasive aspergillosis almost always occurs in the severely immunocompromised patient, most commonly granulocytopenic acute leukemic patients. The presence of pulmonary infiltrates in a febrile, neutropenic patient already on broad-spectrum antibiotic therapy should signal the diagnosis of fungal disease. Pathologically, the disease is characterized by vascular invasion and thrombosis, which leads to hemorrhagic infarction. Over time, with retraction of the infarcted center and peripheral resorption of necrotic tissue by leukocytes, a central area of devitalized tissue is formed. The "air crescent" sign results when air fills the space between the devitalized tissue and the surrounding parenchyma.14 Characteristic CT findings consist of nodules surrounded by a halo of ground-glass attenuation or pleura-based, wedge-shaped areas of consolidation.8 The air crescent sign in angioinvasive aspergillosis is usually seen during convalescence, 2 to 3 weeks after initiation of treatment and reflects returning of host immunocompetence (Fig. 4).



Chest wall involvement in aspergillosis usually begins with a focus of lung infection, which then spreads directly to an adjacent rib or thoracic vertebra. Uncommonly, there may be hematogenous spread to the bone. The pattern of bone destruction is characteristically permeative. Pulmonary aspergillosis in children with chronic granulomatous disease, an inherited disorder of phagocytic cells tends to involve the chest wall and consequently carries a high mortality rate.15

Finally, ABPA affects patients with intact immune systems and usually begins in childhood and is more accurately thought of as a hypersensitivity reaction to airway colonization without tissue invasion. Approximately 96% of patients with ABPA will have symptoms of asthma. Bronchiectatic or normal bronchi are commonly impacted with mucus, hyphae, and debris. The impaction may extend from the proximal bronchi into the second-, third-, or fourth-order bronchi, and this produce a "gloved-finger" or tubular "branching" radio densities.16 In asthmatic patients, findings of bronchiectasis affecting 3 or more lobes, centrilobular nodules, and mucoid impaction on high-resolution CT are highly suggestive of ABPA.17

Our case demonstrates the full spectrum of thoracic aspergillus with gradual evolution from an aspergilloma to a semi-invasive form with eventual invasive aspergillosis manifest as direct involvement of the chest wall, mediastinum, ribs, and thoracic spine. This case is illustrative because of patient's history of treated nonsmall cell lung carcinoma. The radiated lung in the right upper lobe was an area of devitalized tissue, resulting in the optimal environment for opportunistic infections. Involvement of the spine with epidural involvement, as seen in this patient is an uncommon manifestation of aspergillosis. The imaging findings of aspergillus osteomyelitis are nonspecific, and the differential includes TB, staphylococcal osteomyelitis, and other fungal infections. Diagnosis depends on a high index of suspicion and requires aggressive tissue sampling. This case demonstrates the importance of including specific infectious etiologies in the differential diagnosis when chest wall invasion, and bone destruction are identified in patients with a history of malignancy.

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