*INFEKSI JAMUR PADA PARUDepartemen Pulmonologi dan Ilmu Kedokteran RespirasiFKUSU/RSUP H Adam Malik Medan

*Fungi as Infectious AgentsFungi is widely distributed in air, dust, and normal flora.Humans are relatively resistant.Fungi are relatively nonpathogenic.Of the 100,000 fungal species, only 300 have been linked to disease.Fungi are the most common plant pathogens.Human mycoses are caused by true fungal pathogens and opportunistic pathogens.

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*Primary true fungal pathogen can invade and grow in a healthy, noncompromised host.Most striking adaptation to survival and growth in the human host is the ability to switch from hyphal cells to yeast cells.Thermal dimorphism grow as molds at 30C and as yeasts at 37C

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*Emerging Fungal PathogensOpportunistic fungal pathogen has little or no virulence; host defenses must be impaired.Vary from superficial and colonization to potentially fatal systemic disease An emerging medical concern; account for 10% of all nosocomial infectionsDermatophytes may be undergoing transformation into true pathogens.

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*Epidemiology of the MycosesMost fungal pathogens do not require a host to complete their life cycles and infections are not communicable.Dermaphytes and Candida sp naturally inhabit human body and are transmissible.True fungal pathogens are distributed in a predictable geographical pattern - climate, soil.Dermaphytoses most prevalentCases go undiagnosed or misdiagnosed.Systemic, subcutaneous, cutaneous or superficial infections

*Pathogenesis of the FungiPortal of entry primary mycoses respiratory portal; inhaled sporessubcutaneous - inoculated skin; traumacutaneous and superficial contamination of skin surfaceVirulence factors thermal dimorphism, toxin production, capsules and adhesion factors, hydrolytic enzymes, inflammatory stimulants

*Antifungal defenses are the integrity of the barriers and respiratory cilia.Most important defenses are cell-mediated immunity, phagocytosis, and inflammation.Long-term immunity can only develop for some.

*Diagnosis of Mycotic InfectionsDiagnosis and identification require microscopic examination of stained specimens, culturing in selective and enriched media and specific biochemical and serological tests.

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*Control of Mycotic InfectionsImmunization is not usually effective.Control involves intravenous amphotericin B, flucytosine, azoles and nystatin.In some cases surgical removal of damaged tissuesPrevention limited to masks and protective clothing to reduce contact with spores

*SYSTEMIC INFECTIONS BY TRUE PATHOGENSHistoplasma capsulatumCoccidioides immitisBlastomyces dermatitidisParacoccidioides brasiliensis

*Histoplasmosis: Ohio Valley FeverHistoplasma capsulatum most common true pathogen; causes histoplasmosisDistributed worldwide, most prevalent in eastern and central regions of USGrows in moist soil high in nitrogen contentInhaled conidia produce primary pulmonary infection that may progress to systemic involvement of a variety of organs and chronic lung disease.Amphotericin B, ketoconazole

PORTAL OF ENTRY

INHALATION

INOCULATION(rare)

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CauseSpores trapped by macrophagesgerminate in lungsInfection spreads through body in blood stream

Acute Symptoms

Chronic Symptoms5% of those who are infectedChronic histoplasmosis

Disseminated Symptoms

Other SymptomsEnlarged LiverSpleenAdrenal glandJoint painRashesSkin nodules tender red lumps erythema nodosum

DiagnosisFungal cultureFungal stainBlood testChest X-ray distinct markings on lungsCT scanTransbronchial biopsy

CLINICAL SPECIMENSSPUTUMBONE MARROWBIOPSY MATERIALBRONCHIAL WASHINGSPERIPHERAL BLOODGASTRIC WASHINGS

Identification

1. Microscopic observation

2. Conversion

3. DNA Probe

SEROLOGICAL TESTCOMPLEMENT FIXATIONMYCELIAL FORM ANTIGENYEAST FORM ANTIGENIMMUNODIFFUSIONH = ACUTE INFECTIONM = PAST, PRESENT OR SKIN TEST

SEROLOGICAL TESTSEIA detects antibody

EIA to detect ANTIGEN (systemic disease)

ECOLOGICAL ASSOCIATION

Blackbird roosts Bats Bat guano Chicken houses

TreatmentAntifungal drugsIVAmphotericin B (Fungizone IV, Abelcet)OralItraconazole (Sporanox)Ketoconazole

PreventionMinimize exposure to dust in contaminated environmentsChicken coopsBat cavesWear breathing apparatusMasksSpray contaminated soil

COCCIDIOIDOMYCOSIS

COCCIDIOIDOMYCOSISIt may occur as either an acute, benign, self-limited disease or a chronic, malignant disseminated disease involving the cutaneous, subcutaneous, visceral or osseous tissue.

*Coccidioidomycosis: Valley FeverCoccidioides immitis - causes coccidioidomycosisDistinctive morphology blocklike arthroconidia in the free-living stage and spherules containing endospores in the lungsLives in alkaline soils in semiarid, hot climates and is endemic to southwestern U.S.Arthrospores inhaled from dust, creates spherules and nodules in the lungsAmphotericin B treatment

PORTAL OF ENTRY

INHALATION

INOCULATION(Rare)

Pulmonary SymptomsAnorexiaShortness of breathWeight lossProductive cough Night sweatsArthralgiaErythema multiforme

ECOLOGICAL ASSOCIATIONDesert soilArcheological middensPotteryRodent burrowsCottonConstruction sites

SPHERULEENDOSPORESARTHROCONIDIASOILANIMALHUMAN____________

CLINICAL SPECIMENS

SputumPusGastric washingsCSFBronchial washingsBiopsy material

SEROLOGICAL TESTS

Complement fixation Immunodiffusion Slide agglutination EIA

DRUGS OF CHOICE

Fluconazole(mild infection)Itraconazole(mild infection)Amphotericin B (severe infections)

PARACOCCIDIOIDOMYCOSISA chronic granulomatous disease of the lungs, mucous membranes, skin and lymph nodes.

ECOLOGICAL ASSOCIATION Probably soil Armadillos

Paracoccidioidomycosis Triad

Pulmonary lesion

Cervical adenopathy

Edentulous

Paracoccidioidomycosis Triad

Pulmonary lesion

Paracoccidioidomycosis TriadPulmonary lesions

Cervical adenopathy

Prolonged latency

10 20 years

CLINICAL SPECIMENS

SputumBiopsy materialPus CrustsBronchial washings

SEROLOGICAL TESTIMMUNODIFFUSION

Sensitivity - 99 % Specificity - 84 %

DRUGS OF CHOICE

Amphotericin BSulphonamide-trimethoprimItraconazoleVoriconazole

*Blastomyces dermatitidis: North American BlastomycosisBlastomyces dermatitidis- causes blastomycosisDimorphicFree-living species distributed in soil of a large section of the midwestern and southeastern U.S.Inhaled 10-100 conidia convert to yeasts and multiply in lungsSymptoms include cough and fever.Chronic cutaneous, bone, and nervous system complicationsAmphotericin B

*OPPORTUNISTIC MYCOSESMost important fungal pathogens:

Candida AspergillusCryptococcusPneumocystisRhizopusMucorAbsidia

*Infections by Candida: CandidiasisCandida albicansWidespread yeastInfections can be short-lived, superficial skin irritations to overwhelming, fatal systemic diseases.Budding cells of varying size that may form both elongate pseudohyphae and true hyphaeForms off-white, pasty colony with a yeasty odor

*Candida albicansNormal flora of oral cavity, genitalia, large intestine or skin of 20% of humansAccount for 80% of nosocomial fungal infectionsAccount for 30% of deaths from nosocomial infectionsThrush occurs as a thick, white, adherent growth on the mucous membranes of mouth and throatVulvovaginal yeast infection painful inflammatory condition of the female genital region that causes ulceration and whitish dischargeCutaneous candidiasis occurs in chronically moist areas of skin and in burn patients

Clinical manifestations of pulmonary candidiasisCough productive of purulent sputum, dyspnea, and fever The entirely nonspecific manifestations of pulmonary involvement help to explain why it is often not diagnosed until autopsy A typical case would be a patient with faradvanced cancer developing a terminal mixed pneumonia with bacteria and Candida

Chest roentgenograms of pulmonary candidiasis patchy or lobar infiltrates

*Diagnosis and TreatmentPresumptive diagnosis made if budding yeast cells and pseudohyphae are found; germ tubeGrowth on selective, differential media differentiates Candida speciesTopical antifungals for superficial infections, amphotericin B and fluconazole for systemics

*Cryptococcosis and Cryptococcus neoformansCryptococcus neoformans causes cryptococcosis.A widespread encapsulated yeast that inhabits soil around pigeon roosts Common infection of AIDS, cancer or diabetes patientsInfection of lungs leads to cough, fever, and lung nodulesDissemination to meninges and brain can cause severe neurological disturbance and death.

*Diagnosis and TreatmentNegative stain demonstrating encapsulated budding yeastBiochemical tests, serological testingSystemic infection requires amphotericin B and fluconazole.

*Pneumocystis (carinii) jiroveci and Pneumocystis PneumoniaA small, unicellular fungus that causes pneumonia (PCP), the most prominent opportunistic infection in AIDS patientsThis pneumonia forms secretions in the lungs that block breathing and can be rapidly fatal if not controlled with medication.Pentamidine and cotrimoxazole

ASPERGILLOSISAspergilloma. (Fungus ball)ABPA. (Hypersensitivity)Aspergillus necrotizing bronchitis. endo-bronchial mass, obstructive pneumonitis, collapse, hilar mass.Invasive Pulmonary Aspergillosis. Angioinvasive/ hemorrhagic infarcts. Airway invasive-obstructing.

Saprophytic Aspergillosis (Aspergilloma )Review of 60.000 CXR indentified 0.01 % prevelance.Infection without tissue invasion. Solid rounded mass, some times mobile.Fungal hyphae mixed with mucus and cellular debris within a preexistent pulmonary cavity or ectatic bronchus .If peripheral, Pleural thickening is characteristic.Mass is usually seperated from the cavity wall.

Saprophytic Aspergillosis (Aspergilloma )Clinical findings could be non-specific.Some patients may remain asymptomatic.Most frequent symptom is HEMOPTYSIS 75%.Less commonly chest pain, dyspnea , malaise.Wheezing and fever (could also be secondary to underlying disease, or bacterial super infection of the cavity or aspergilloma itself).

AspergillomaThe most common predisposing factors are tuberculosis and sarcoidosis. Other conditions that occasionally may be associated with aspergilloma include bronchogenic cyst, pulmonary sequestration, and pneumatoceles secondary to Pneumocystis carinii pneumonia in patients with (AIDS) .Bronchiectasis, ankylosing spondylitis, neoplasm.

AspergillomaTuberculosis is the most frequently associated condition.Aspergilloma with history of tuberculosis. May show multiple irregular fungus balls virtually filling the pulmonary cavity

Aspergilloma RadiographyPresence of a solid, round or oval mass with soft-tissue opacity within a lung cavity.Mass is separated from the wall of the cavity by an airspace of variable size and shape "air crescent" sign seen in thin section CT (mediastinal window).Other causes of the air crescent sign include angioinvasive aspergillosis, echinococcal cyst, and, rarely, tuberculosis, lung abscess, bronchogenic carcinoma, hematoma, and P carinii pneumonia.

AspergillomaAspergillomas are often associated with thickening of the cavity wall and adjacent pleura.Pleural thickening may be the earliest radiographic sign before any visible changes are seen within the cavity.Associated scarring in lung lobes.Aspergillomas are usually single, they may also be present bilaterally.Change in position.

CT

AspergillomaMobile aspergillomaThe aspergilloma usually moves when the patient changes position .Chest CT scans obtained with the patient supine and prone show a change in the position of the aspergilloma within a pulmonary cystic cavity.

Mobile aspergilloma within a pulmonary cystic cavity in a 43-year-old man. Chest CT scans obtained with the patient supine (a) and prone (b) show a change in the position of the aspergilloma. A fumigatus was discovered at bronchoscopy. (Courtesy of Josep M. Mata, MD, Unidad Diagnstica de Alta Tecnologa, Sabadell, Spain.)

Aspergilloma TreatmentIn asymptomatic patients, No therapy needed.Medical therapy with bed rest, humidified oxygen, cough suppressant, and postural drainage is helpful in cases of mild hemoptisis.Surgical resection is indicated for patients with severe life-threatening hemoptysis.Selective bronchial artery embolization can be performed in those with poor lung function.

Aspergilloma Antifungal therapyPatient is not a candidate for surgeryConcomitant tissue invasionItraconazole with some helpAmpho B for invasive component.Newer Azoles, Voriconazole , Posaconazole , and Ravuconazole.Their role is not clear.Antibiotics for bacterial superinfection.

Hypersensitivity Reaction (Allergic Bronchopulmonary Aspergillosis) ABPA is seen most commonly in patients with long-standing bronchial asthma (7-14%) or CF (6%) .Characterized by the presence of plugs of mucus containing Aspergillus organisms and eosinophils. This results in bronchial dilatation typically involving the segmental and sub segmental bronchi.

Allergic Bronchopulmonary AspergillosisABPA is caused by a complex hypersensitivity reaction to Aspergillus organisms. The fungi proliferate in the airway lumen , producing a constant supply of antigen. A type I hypersensitivity reaction with IgE and IgG release occurs.Immune complexes and inflammatory cells are then deposited in the bronchial mucosa.Production of necrosis and eosinophilic infiltrates (type III reaction) with bronchial wall damage and bronchiectasis.

Allergic Bronchopulmonary AspergillosisExcessive mucus production and abnormal ciliary function lead to mucoid impaction. Many patients cough up thick mucous plugs in which hyphal fragments can be demonstrated at culture or histologic analysis.Acute clinical symptoms include recurrent wheezing, malaise with low-grade fever, cough, sputum production, and pleuritic chest pain.Patients with chronic ABPA may also have a history of recurrent pneumonia.

Allergic Bronchopulmonary Aspergillosis Radiologic manifestationsHomogeneous, tubular, finger-in-glove areas of increased opacity in a bronchial distribution, usually predominantly involving the upper lobes. Band like opacities related to plugging of airways by hyphal masses with distal mucoid impaction and can migrate from one region to another. Occasionally, isolated lobar or segmental atelectasis may occur.

Allergic Bronchopulmonary AspergillosisIn later stages central bronchiectasis and pulmonary fibrosis develop. CT findings in ABPA consist primarily of mucoid impaction and bronchiectasis involving predominantly the segmental and sub segmental bronchi of the upper lobes . In approximately 30% of patients, the impacted mucus has high attenuation or demonstrates frank calcification at CT.

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Allergic Bronchopulmonary Aspergillosis Diagnostic criteriaAsthma.Immediate skin reactivity to Aspergillus.Serum precipitins to A fumigatus.Total serum IgE >1.000 ng/mlCurrent or previous pulmonary infiltrates.Central Bronchiectasis.Peripheral Eosinophilia.

Allergic Bronchopulmonary Aspergillosis Stages /Patterson et allStage 1 ( Acute stage)Stage 2 ( Remission stage)Stage 3 ( Exacerbation stage)Stage 4 ( Steroid dependent stage)Stage 5 ( Fibrotic stage)

Allergic Bronchopulmonary Aspergillosis TreatmentOral corticostroids, relief of bronchospasm, clearing of pulmonary infiltrates and decrease IgE levels( 0.5 mg/kg/d for 2 wks then taper).Most patients require prolonged low dose therapy.Itraconazole low dose(200 mg bid for 16 weeks) can Help in 50% reduction of corticosteroid dose. With no significant toxicity.

Allergic Bronchopulmonary Aspergillosis Syndromes Related to ABPAMucoid Impaction Without asthma, mucus plug lead to atelectasis. Usually presents with cough.Bronchocentric Granulomatosis. Necrotizing granulomas, obstruct and destroy bronchiols . Eosinophilic inflamatory infiltrate and fibrosis with no tissue or vascular invasion by aspergillus, almost always asthmatics with persistent cough and high IgE levels. good response to corticosteroids.

Allergic Bronchopulmonary AspergillosisEosinphilic pneumonitis Rarely caused by aspergillus, cough dyspnea and fever with peripheral pulmonary infiltrate, diagnosis made by biopsy, good response to corticosteroids.Hypersesitivity pneumonitis Extrinsic allergic alveolitis, intense repeated inhalation of thermophilic bacteria, fungi, bird excreta, and chemical agents causes hypersensitivity granulomatous inflamation of distal airway disease.

Semi-invasive (Chronic Necrotizing) Aspergillosis Predisposing factors Chronic debilitating illness, Advanced age. Alcoholism, Malnutrition.DM, CF, COPD.Prolonged steroid therapy, Radiation therapy.Inactive TB.Pneumoconiosis.Sarcoidosis.

Semi-invasive (Chronic Necrotizing) Aspergillosis SymptomsOften insidious and include chronic cough, sputum production, fever, and constitutional symptoms.Hemoptysis has been reported in 15% of affected patients . May manifest with chronic bronchitis and recurrent episodes of mild hemoptysis.

Semi-invasive (Chronic Necrotizing) AspergillosisIn patients with COPD, may manifest with non-specific clinical symptoms such as cough, sputum production, and fever lasting more than 6 months.

Semi-invasive (Chronic Necrotizing) Aspergillosis Radiologic manifestations Thin-section CT scan (lung window) shows unilateral or bilateral rounded segmental areas of consolidation with or without cavitation or adjacent pleural thickening, Multiple nodular areas of increased opacity .The findings progress slowly over months or years.

Semi-invasive (Chronic Necrotizing) Aspergillosis Diagnosis CriteriaClinical and Radiologic featuresIsolation of Aspergillus species by culture from sputum, bronchoscopic or percutaneous samples.Exclusion of other conditions

Semi-invasive (Chronic Necrotizing) Aspergillosis TreatmentAntifungals should be initiated once the diagnosis is made. IV Ampho B, Itraconazole is also effective.Surgical resection for healthy individuals with good lung reserves, not tolerating antifungals or where antifungals are ineffective in setting of active disease.

Invasive Pulmonary Aspergillosis (IPA) Major risk factors.Prolonged neutropenia >3 wks or neutrophil dysfunction.Corticosteroid therapy (prolonged, high dose).Transplantation (Lung and BM )Hematologic malignancy( leukemia)Cytotoxic therapy.AIDS.

Airway-invasive Aspergillosis The presence of Aspergillus organisms deep to the airway basement membrane. It occurs most commonly in immunocompromised neutropenic patients and in patients with AIDS. Clinical manifestations include acute tracheobronchitis, bronchiolitis, and bronchopneumonia.

Airway-invasive AspergillosisPatients with acute tracheobronchitis usually have normal radiologic findings. Occasionally, tracheal or bronchial wall thickening may be seen.Bronchiolitis is characterized at HRCT by the presence of centrilobular nodules and branching linear or nodular areas of increased attenuation having a "tree-in-bud appearance.

Airway-invasive AspergillosisThe centrilobular nodules have a patchy distribution in the lung. Aspergillus bronchopneumonia results in predominantly peribronchial areas of consolidation. Rarely, the consolidation may have a lobar distribution.

Airway-invasive Aspergillosis Obstructing bronchopulmonary aspergillosisnoninvasive form of aspergillosis.Characterized by the massive intraluminal overgrowth of Aspergillus species.Usually A fumigatus, in patients with AIDS . Affected patients exhibit cough, fever, and new onset of asthma.Patients may cough up fungal casts of the bronchi and present with severe hypoxemia.

Airway-invasive Aspergillosis CT findings in obstructing bronchopulmonary aspergillosisMimic those in allergic bronchopulmonary aspergillosis.Bilateral bronchial and bronchiolar dilatation.large mucoid impactions (mainly lower lobes).Diffuse lower lobe consolidation caused by postobstructive atelectasis.

Angioinvasive Aspergillosis Angioinvasive aspergillosis occurs almost exclusively in immunocompromised patients with severe neutropenia. For many reasons, however, there has been a substantial increase in the number of patients at risk for developing invasive aspergillosis.

Angioinvasive Aspergillosis These reasons includesDevelopment of new intensive chemotherapy regimens for solid tumors.Difficult-to-treat lymphoma, myeloma, and resistant leukemia.Increase in the number of solid organ transplantations.Increased use of immunosuppressive regimens for other autoimmune diseases.

Angioinvasive AspergillosisDespite having a normal neutrophil count, affected patients have functional neutropenia because the function of the neutrophils is inhibited by the use of high-dose steroids.Invasion and occlusion of small to medium-sized pulmonary arteries by fungal hyphae. This leads to the formation of necrotic hemorrhagic nodules or pleura-based, wedge-shaped hemorrhagic infarcts.

Angioinvasive Aspergillosis Characteristic CT findings Nodules surrounded by a halo of ground-glass attenuation "halo sign or pleura-based, wedge-shaped areas of consolidation. These findings correspond to hemorrhagic infarcts.In severely neutropenic patients, the halo sign is highly suggestive of angioinvasive aspergillosis.

Angioinvasive AspergillosisHowever, a similar appearance has been described in a number of other conditions.Infection by Mucorales and Candida.Herpes simplex and cytomegalovirus.Wegener granulomatosis, Kaposi sarcoma , and hemorrhagic metastases .

Angioinvasive AspergillosisSeparation of fragments of necrotic lung from adjacent paren-chyma results in air crescents similar to those seen in mycetomas. The air crescent sign in angioinvasive aspergillosis is usually seen during convalescence (ie, 23 weeks after initiation of treatment and concomitant with resolution of the neutropenia).

Angioinvasive Aspergillosis DiagnosisThe clinical diagnosis is difficult, and the mortality rate is high.Positive culture Methanamine silver, PASBAL 97% specific. But less sensitive.Chest CT findings, Halo sign, Cresent sign.Open or thoracoscopic lung biopsy is the gold standard.

Invasive Pulmonary Aspergillosis (IPA) TreatmentStart empiric therapy, when diagnosis suspected.Most commonly used medicine Ampho B 0.6 1.2 mg/kg/d , in severly immunocomromized 1 -1.5 mg/kg/d.Duration depends on the period of immunosuppression. response 20-83%.

Invasive Pulmonary Aspergillosis (IPA)Other treatment optionsItraconazol 200-400 mg/d , 39% response.Could be used in less immunocompromised.Late stage therapy after initial control of Ampho B.Combination therapy , no great efficacy.Caspofungin ,recently approved medicine.Voriconazole, Posaconazole.

Invasive Pulmonary Aspergillosis (IPA)Voriconazole vs Ampho B, (391 pt randomized ). Succesfull response rate 49.7% for Vorico arm, 27.8% for Ampho B. Herbrecht et al, NEM 347: 408 (2002).Caspofungin, 70% favorable response in pulm. disease for salvage therapy, daily dose. Ampho B + Caspo , Vori + Caspo, combination better out come. marr et al, clin inf . Dis 2003.

Invasive Pulmonary Aspergillosis (IPA) Surgical resectionMassive hemoptysis.Localized lesion.Continuing immunosuppression.Further immunosuppressive therapy.Outcome is poor in BMT, Pt on mechanical ventilation and those who have multiple foci of infection.

Invasive Pulmonary Aspergillosis (IPA)Outcome of therapyEarly diagnosis.Recovery of underlying host defense defect.Resolution of neutropenia,Taper of immunosupressive therapy.Disease limited to the lung.

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Macrophages: immune system cells that attack foreign organismscarry the spores to lymph nodes in chestcontinue to multiplymay lead to inflammation, scarring and calcium deposits heavy infection: lymph nodes may become so enlarged that they obstruct esophagus/lungs' airways

**may resemble Tuberculosis *Anemia: decrease in red blood cells or less quantity of hemoglobin in blood**Fungal Culture: several weeks to confirm diagnosis, test isn't used when immediate treatment is neededBlood Test: AntibodiesChest X-ray: single pulmonary nodule of histoplasmosisTransbronchial biopsy: bronchoscope is inserted through the nose or mouth to collect several pieces of lung tissue

*Amphotericin B to briefly start if serious, then followed by an oral antifungal***Bilateral pulmonary cavities in the upper lungs surrounded by circumferential pleural thickening and containing aspergillomas*CT scan shows normal pleural thickness in the right upper lobe cavity as well as a left intracavitary aspergilloma with associated pleural thickening*Photograph of an autopsy specimen from the left upper lobe shows an irregular cavitary lesion with regular margins and a dark brown appearance caused by necrotic material and superimposed Aspergillus infection.*(a) Chest CT scan (mediastinal window) obtained at the level of the carina shows a thickened, narrowed right main bronchus with associated right upper lobe collapse.

*(b) Bronchoscopic image shows elevated, whitish mucosal lesions in the right main bronchus (arrow).*(c) High-power photomicrograph (original magnification, x400; hematoxylin-eosin stain) of a biopsy specimen from the right upper lobe reveals massive Aspergillus hyphae invading the bronchial epithelium (arrows).

*Obstructing bronchopulmonary aspergillosis in a 29-year-old man with AIDS. CT scan shows multiple rounded and tubular areas of increased attenuation in both lower lobes, findings that are consistent with mucus-filled airways. Bronchoscopy revealed that the lumen was packed with inflammatory material.

*Angioinvasive aspergillosis in a 42-year-old man with acute myelogenous leukemia. (a) Chest CT scan (lung window) reveals a 2-cm nodular lesion with a wide halo of ground-glass attenuation representing adjacent hemorrhage.*(b) Photograph of a cut section of the lung demonstrates a rounded tan nodule, a finding that is consistent with pulmonary infarction.

*(c) Low-power photomicrograph (original magnification, x40; hematoxylin-eosin stain) shows vascular invasion by Aspergillus species (arrows).

*>>>>>>Cutaneous Kaposi sarcoma in a 34-year-old homosexual man with AIDS. Thin-section CT scan shows multiple hemorrhagic pulmonary nodules with an associated halo sign.

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