Imaging in Fungal Infections of Chest

Dr. Gobardhan ThapaResident, First yearRadiodiagnosis,NAMS, Bir HospitalNepal

Outline of Presentation

• Introduction• Classification of Fungal Infections• Overview of specific Fungal organism and the

current Imaging modalities• Summary• references

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.

• 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.

Chest computed tomographic (CT) scan

-Journal of Zhejiang university science, April, 2014

• 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

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

Fungal Infections:

Saprophytic FungiCandidiasisPneumocystisCryptococcosisMucormycosisAspergillus

Pathogenic FungiHistoplasmosisCoccidioidomycosisBlastomycosisParacoccidioidomycosis

In all cases, fungi elicit a “Necrotizing granulomatous reaction”

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

• 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

Fig. acute histoplasmosiswidespread bilateral well-defined 3-5 mm nodules

Fig. disseminated histoplasmosis in a HIV patientaxial CT shows multiple small pulmonary nodules distributed

uniformly throughout the both lungs

Fig. Histoplasmosis incidental finding of multiple calcified

pulmonary nodules

• 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

Fig. HistoplasmomaAxial CT shows right lower lobe Histoplasmoma with central calcification

Fig. fibrosing mediastinitis following Histoplasmosisradiographs shows widening of the mediastinum

• blood-borne dissemination– Asymptomatic blood-borne dissemination is common– Eg calcified granulomas in patients of endemic area

– Clinically apparent disseminated histoplasmosis• Extremely rare

2. Coccidioidomycosis

• Coccidioides immitis• Found in soil in arid/semi-arid areas• 4 types of clinical and radiographic pulmonary

infections:a) Acute Coccidioidomycosisb) Persistent Coccidioidomycosisc) Chronic progressive diseased) Disseminated (Miliary) Coccidioidomycosis

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

b) 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

c) Chronic progressive disease• Upper lobe fibro-cavitatory disease

– Thin-walled cyst : Grape-skin sign• Similar to Post-primary TB and Histoplasmosis

d) Disseminated (Miliary) coccidioidomycosis• Relatively rare• Affects the immuno-compromised patients

Fig. coccidioidomycosisa non-specific patch of consolidation present in left lower

lobe. One year later a thin-walled cavity is evident

Fig. primary coccidioides infectionfrontal 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

Fig. primary coccidioides infectioncoronal reformatted CT of same patient

confirms a right middle lobe nodule

Fig. Chest x-ray showing Grape-skin signthin-walled grape-skin cyst

over time cavity may deflate and acquire slightly thicker wall

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

• 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

• Less common presentation:– Diffuse reticulo-nodular opacities

• Pleural effusion and lymph node enlargement – uncommon

• Disseminated miliary form– In immunocompromised hosts

Fig. Blastomyces dermatidis infectionchest 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

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

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

• 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

Fig. disseminated candidiasis with CT halo sign

6. Pneumocystis jiroveci

• Opportunistic fungal pathogen• Cause pneumonia in patients with – AIDs– Organ transplant– Undergoing chemotherapy– Immunosuppressive treatment– Long term corticosteroids

• 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

Fig. Pneumocystis Pneumonia in an HIV patient: Crazy paving sign

• Complications:– Thin-walled cavities– Pneumothorax

• Less common presentations– pleural effusion, nodules, miliary disease, calcified

lymph nodes

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)

• 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

Fig. cryptococcusa pleurally based mass like area of consolidation in the left

upper lobe is present in a patient who also had cryptococcal meningitis

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

• 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

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

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

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

• 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

Fig. Air-crescent or Monad sign of Aspergillusgravity dependence of fungus ball

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

Fig. aspergillosisa necrotizing pneumonia in both lower zones has cavitated mimicking the formation of fungus balls

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

Halo sign: Angio-Invasive aspergillosisPA radiograph and axial CT image show right upper lobe mass with peripheral ground

glass opacity constituting Halo sign

• Broncho-invasive:– In patients with severe

neutropenia and in patients with AIDS

– Chest X-ray: large nodular opacities to diffuse parenchymal consolidation

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

Fig. chest x-ray PA view: branching tubular opacities emanating from the hila -

FINGER-IN-GLOVE appearance

• 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

Fig. allergic broncho-pulmonary aspergillosisNECT axial (left) and oblique sagittal (right) chest

Fig. allergic bronchopulmonary aspergillosisHRCT scan demonstrating finger-like opacities due

to dilated mucus-filled bronchi

SummaryFungal pneumonia Specific imaging findings

1 Histoplasmosis • Central, lamellated or diffuse calcification of a nodule < 3 cm virtually diagnostic

• Acute histoplasma pneumonia: Airspace opacities any lobe, solitary or multiple; usually lower lungs

• Ipsilateral hilar mediastinal lymphadenopathy• Fibrosing mediastinitis

2 Coccodioidomycosis Cavitating segmental or lobar consolidation in an endemic area Solitary or multifocal segmental or lobar consolidation Solitary or multiple lung nodulesMediastinal and hilar nodes

3 Blastomycosis • Airspace disease or mass in an outdoorsman from an endemic area

• Cavitation

Fungal pneumonia Specific imaging findings

4 Paracoccidioidomycosis • Areas of ground glass opacities, interlobular septal thickening, consolidation, cavitation and fibrosis

5 Candidiasis Chronic pneumonia, abscess, mycetoma formationMultiple bilateral nodular opacities with areas of consolidation and ground glass opacities

6 Pneumocystis Peri-hilar ground-glass opacited in a patchy or geographic distribution with thickened septa

Fungal pneumonia Specific imaging findings

7 Cryptococcosis Homogeneous segmental or lobar opacificationsMiliary, reticular or reticulo-nodular interstitial patterns

8 Mucormycosis Lobar or multilobar areas of consolidationcavitation

9 Aspergillus Aspergilloma of mycetoma formationChronic necrotizing aspergillosisBroncho-invasive with diffuse parenchymal consolidationNecrotic nodules surrounded by ground glass attenuaiton- halo signABPA with non-segmental areas of opacities mainly in upper lobes, branching thick tubular opacities due to bronchi distended with mucus- finger-in-glove appearance

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

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

Thank you