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Imaging in Fungal Infections of Chest Dr. Gobardhan Thapa Resident, First year Radiodiagnosis, NAMS, Bir Hospital Nepal
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Outline of Presentation Introduction Classification of Fungal Infections Overview of specific Fungal organism and the current Imaging modalities Summary references
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A case report A 71-year-old Chinese male was admitted with complaint of chronic cough and malaise for two months. He had been in Tucson, Arizona, USA, visiting for four months right before the symptoms occurred. He had transient low-grade fever, but denied hemoptysis, night sweats, skin rashes, or headache. He did not smoke or abuse drugs. Physical examination revealed no abnormalities. Lab tests showed an elevated erythrocyte sedimentation rate (ESR) of 46 mm/h, while complete blood count (CBC), eosinophil count, serum chemistry, and tumor biomarkers were all in normal range. Human immunodeficiency virus (HIV) antibody was found to be negative. Sputum culture showed normal flora growth.
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Chest computed tomographic (CT) scan revealed an irregular-margined opacity measuring 3.0 cm×3.8 cm in diameter in the sub-pleura region of right middle lobe. Right hilar and mediastinal lymphadenopathy was noted. Lung cancer was considered as the most likely diagnosis. Subsequent bronchoscopy and brush cytology were negative. The patient received a procedure of right middle lobe and lower lobectomy on the eighth day after admission.
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Chest computed tomographic (CT) scan
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Histopathological examination of lung specimen showed focal necrotic granulomatous inflammation with multinucleated giant cells containing fungal spherules and infiltrations of massive neutrophils, eosinophils, and lymphocytes.. The final diagnosis thus was confirmed pathologically as pulmonary Coccidioides infection. The patient was totally free from discomfort in the course of two years follow- up after the lobectomy -Journal of Zhejiang university science, April, 2014
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Introduction Fungal Pneumonia Are now seen with increased frequency Increase in the incidence of disease caused by pathogenic fungi in healthy hosts Emergence of opportunistic species in immuno- compromsied hosts
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Fungal Infections: Saprophytic Fungi Candidiasis Pneumocystis Cryptococcosis Mucormycosis Aspergillus Pathogenic Fungi Histoplasmosis Coccidioidomycosis Blastomycosis Paracoccidioidomycosis In all cases, fungi elicit a “Necrotizing granulomatous reaction”
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1. Histoplasmosis Histoplasma capsulatum In moist soil and bird/bat excreta Mostly subclinical infection: Heals spontaneously CXR: may be normal Or sometimes well-defined, calcific nodules <1 mm in size Calcified hilar of mediastinal nodes Multiple miliary calcified nodules
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Progression of the infective foci: Leading to a larger nodule Hilar nodes enlargement is common Locally progressive: may have consolidative changes, later associated with Fibrosis and cavitation. Massive inhalation of organisms: May show fairly discrete, nodular opacities 3-4 mm in diameter with hilar adenopathy
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Fig. acute histoplasmosis widespread bilateral well-defined 3-5 mm nodules
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Fig. disseminated histoplasmosis in a HIV patient axial CT shows multiple small pulmonary nodules distributed uniformly throughout the both lungs
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Fig. Histoplasmosis incidental finding of multiple calcified pulmonary nodules
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Histoplasmoma: A solitary, sharply defined nodule <3 cm Most common in lower lobes-frequently calcify Fibrosing Mediastinitis (chronic pulmonary disease): Uncommon late manifestation Stenosis of venacava, oesophagus, trachea, bronchi or central pulmonary vessels CXR: widened mediastinum
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Fig. Histoplasmoma Axial CT shows right lower lobe Histoplasmoma with central calcification
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Fig. fibrosing mediastinitis following Histoplasmosis radiographs shows widening of the mediastinum
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blood-borne dissemination Asymptomatic blood-borne dissemination is common Eg calcified granulomas in patients of endemic area Clinically apparent disseminated histoplasmosis Extremely rare
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2. Coccidioidomycosis Coccidioides immitis Found in soil in arid/semi-arid areas 4 types of clinical and radiographic pulmonary infections: Acute Coccidioidomycosis Persistent Coccidioidomycosis Chronic progressive disease Disseminated (Miliary) Coccidioidomycosis
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a) Acute coccidioidomycosis Develops in 40% of infected adults Self-limiting viral type illness: Valley fever Associated with erythema nodosum and Arthralgia CXR: may be normal or Focal or multifocal segmental air-space opacities Associated with Hilar and mediastinal adenopathy and pleural effusion Persistent coccidioidomycosis (infection beyond 6-8 weeks) Coccidioidal masses or nodules (coccidioidomas) Areas of round pneumonia- subpleural regions of upper lobes Cavitate rapidly-produce characteristic thin-walled cavities
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c) Chronic progressive disease Upper lobe fibro-cavitatory disease – Thin-walled cyst : Grape-skin sign Similar to Post-primary TB and Histoplasmosis Disseminated (Miliary) coccidioidomycosis Relatively rare Affects the immuno-compromised patients
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Fig. coccidioidomycosis a non-specific patch of consolidation present in left lower lobe. One year later a thin-walled cavity is evident
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Fig. primary coccidioides infection frontal radiograph in a female with a clinical diagnosis of valley fever reveals a mass like opacity in the right lower lung with enlarged right hilar nodes
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Fig. primary coccidioides infection coronal reformatted CT of same patient confirms a right middle lobe nodule
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Fig. Chest x-ray showing Grape-skin sign thin-walled grape-skin cyst over time cavity may deflate and acquire slightly thicker wall
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3. Blastomycois Caused by Blastomyces dermatidis Chronic systemic disease Primarily affects the lungs and the skin Pulmonary infections often asymptomatic Symptomatic infection: – Resembles that of an Acute bacterial pneumonia
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Radiographically: Usually non-specific Most common presentation: Homogeneous non-segmental air space opacification with propensity for upper lobes Less common presentation: Single or multiple masses Cavitate in 15% of cases Tend to occur in patients with prolonged symptoms (1 months)-may mimic Bronchogenic Ca
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Less common presentation: Diffuse reticulo-nodular opacities Pleural effusion and lymph node enlargement – uncommon Disseminated miliary form In immunocompromised hosts
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Fig. Blastomyces dermatidis infection chest radiograph shows an ill-defined mass in the left upper lobe. CT scan through the upper lobes shows an irregular mass in the left upper lobe with surrounding ground glass opacity. Biopsy revealed Blastomyces dermatidis infection
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4. Paracoccidioidomycosis(PCM) Also known as South American Blastomycosis Endemic disease caused by dimorphic fungi Paracoccidioides brasiliensis Most frequent systemic mycosis in Latin America esp. in Brazil HRCT: Areas of ground-glass opacities, nodules, interlobular septal thickening, air-space consolidation, cavitation and fibrosis
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5. Candidiasis Candida albicans Important pathogen esp. in Immunocompromised patients: – Particularly in patients with underlying malignancy, IV drugs abuser, AIDS, following Bone marrow transplant Lung infection is usually due to hematogeneous spread
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Radiographically, may present as Chronic pneumonia Abscess formation Mycetoma formation CT Multiple bilateral nodular opacities often associated with areas of consolidation and ground glass opacities-CT halo sign Less common presentations: Pleural effusion, thickening of bronchial walls, cavitation
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Fig. disseminated candidiasis with CT halo sign
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6. Pneumocystis jiroveci Opportunistic fungal pathogen Cause pneumonia in patients with AIDs Organ transplant Undergoing chemotherapy Immunosuppressive treatment Long term corticosteroids
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Radiographically, May have normal findings Classic features: diffuse, bilateral interstitial infiltrates in peri-hilar distribution CT: Done in a highly suspicious case for confirming the diagnosis Peri-hilar ground glass opacities, in a patchy or geographic distribution with areas of superimposed interlobular septal thickening: Crazy Paving pattern May rapidly progress to involve entire lung
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Fig. Pneumocystis Pneumonia in an HIV patient: Crazy paving sign
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Complications: Thin-walled cavities Pneumothorax Less common presentations pleural effusion, nodules, miliary disease, calcified lymph nodes
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7. Cryptococcosis (Torulosis) Cryptococcus neoformans (yeast form fungi) Found in soil or bird droppings Mostly asymptomatic Cryptococcal pneumonia – Common in AIDS (when CD4 <100/cu. mm)
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Chest radiography: Homogeneous, segmental or lobar opacifications Miliary, reticular or reticulo-nodular interstitial patterns Pulmonary masses-5 mm to large (usually pleura- based) with ill-defined edge known as Torulosis May show Halo sign May cavitate Lymph node enlargement and calcification is unusual
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Fig. cryptococcus a pleurally based mass like area of consolidation in the left upper lobe is present in a patient who also had cryptococcal meningitis
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8. Mucormycosis Opportunistic fungal infection of order Mucorales Broad, non-septated hyphae that randomly branch at right angles Spreading destructive infections in Diabetics and immuno-compromised
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Radiographically, Lobar or multi-lobar areas of consolidation and solitary or pulmonary nodules and masses with Cavitation in 26-40 % cases-air crescent sign suggestive of invasive fungal infection in 5-12.5 % cases Dense cavitating bronchopneumonia CT: Non-specific Solitary or multiple areas of consolidation or solitary of multiple nodules surrounded by a Halo of ground-glass attenuation and cavitation
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Fig. pulmonary mucormycosis in a patient reverse halo or bird nest or Atoll sign axial (left) and coronal (right) images show peripheral rim of consolidation surrounding central ground glass opacity, reticulation and nodularity
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9. Aspergillus infection Caused by Aspergillus species, usually A. fumigatus Can take different forms, depending on an individual’s immune response to the organism, classically: Aspergilloma or Mycetoma formation or Saprophytic forms Invasive forms Allergic forms
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Aspergilloma Also known as fungus ball a ball of hyphae, mucus and cellular debris that colonizes a pre-existing bulla or a parenchymal cavity created by some other pathogen or destructive process Invasion into lung parenchyma does not occur unless the host defense mechanisms are compromised Usually asymptomatic May cause Hemoptysis-which can be massive
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Radiographs or CT findings: Solid round mass within an upper lobe cavity, with an area of Air- crescent separating the mycetoma from the cavity wall- roll dependently on decubitus radiographs Progressive apical pleural thickening adjacent to a cavity is common should prompt a search for a complicating mycetoma
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Fig. Air-crescent or Monad sign of Aspergillus gravity dependence of fungus ball
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Semi-invasive or Chronic necrotizing Aspergillosis In patients with mildly impaired immunity e.g. Chronic illness, Diabetes, malnutrition, alcoholism, advanced age, steroid administration, chronic obstructive disease Radiographically- variable appearance Most common: One or more rounded, poorly marginated areas of homogeneous opacification with or without Air-bronchograms and or cavitation With time, the lesions margins may become discrete – May resemble a mass
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Fig. aspergillosis a necrotizing pneumonia in both lower zones has cavitated mimicking the formation of fungus balls
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Invasive Aspergillosis Angio-invasive: Occlusion of small-to-medium pulmonary arteries Developing necrotic hemorrhagic nodules or infarcts CT: Multiple nodules surrounded by a Halo of ground glass attenuation CT HALO sign or Pleural-based wedge-shaped areas of consolidation
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Halo sign: Angio-Invasive aspergillosis PA radiograph and axial CT image show right upper lobe mass with peripheral ground glass opacity constituting Halo sign
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Broncho-invasive: In patients with severe neutropenia and in patients with AIDS Chest X-ray: large nodular opacities to diffuse parenchymal consolidation
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Allergic Bronchopulmonary Aspergillosis (ABPA) A hypersensitivity reaction-occurring in major airways Associated with asthma, elevated serum IgE levels, positive precipitins and skin reactivity to aspergillus Chest X-ray: Non-segmental areas of opacities most common in upper lobes Lobar collapse thick tubular opacities due to bronchi distended with mucus and fungus- Finger-in-gloves sign Occasional cavitation
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Fig. chest x-ray PA view: branching tubular opacities emanating from the hila - FINGER-IN-GLOVE appearance
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CT: Usually, hypodense mucus plugs 20% cases- hyperdense mucus plugs Branching tubular opacities with high attenuation Nearly 30% cases: calcified Recurrent attacks: Pulmonary fibrosis and bronchiectatic changes
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Fig. allergic broncho-pulmonary aspergillosis NECT axial (left) and oblique sagittal (right) chest
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Fig. allergic bronchopulmonary aspergillosis HRCT scan demonstrating finger-like opacities due to dilated mucus-filled bronchi
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Summary
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Role of the radiologists Integrating the clinical data and the radiological data enables in substantial narrowing of the differential diagnosis Need of guided biopsy in selected cases for providing a presumptive final diagnosis, especially when dealing with immuno-compromised patients
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References Text book of Imaging and radiology, David sutton Fundamentals of diagnostic radiology, Brant and Helms Grainger and Allison’s Diagnostic radiology Christopher M. et al, Imaging Pulmonary Infection: classic signs and patterns (2014) American journal of radiology Images from Various websites
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