CT findings in fungal opportunistic pneumonias: body and brain involvement

Compwerized Medical Imaging and Grap~~ics. Vol. 13, No. 5, pp. 423-428, Printed in the U.S.A. All rights reserved.

1989 copyright

0895-61 I l/89 $3.00 + .OU @ 1989 Pergamon Pms.s plc

CT FINDINGS IN FUNGAL OPPORTUNISTIC PNEUMONIAS: BODY AND BRAIN INVOLVEMENT Giuseppe Potente* Institute of Radiology,

“La Sapienza”

University,

Rome, Italy

(Received 7 December 1988) Abstract-A population of 28 immunocompromised hosts with proved pulmonary infections by Cundida species (n = 18) or angloinvasive fungal pneumonias (Aspergillus species, n = 7, Mucor species n = 2, Trichosporon cupita~mn n = 1) were retrospectively examined for any characteristic computed tomographic (Cr) pattern. Chest CT examination in angioinvasive fungal pneumonias (AFP) showed in all cases nodules or mass-like infiltrates. The mass/nodules were surrounded by a halo of low attenuation in early scans (n = 3/10) and showed often a peripheral enhancement in 6/8 contrast-enhanced scans. m abnormalities in AFP were confined to the chest. Of the 18 patients with Candidu pneumonias, 6 showed a mixed air space-interstitial pattern, 4 a granular pattern, 6 some type of mass-l&e consolidation, without neither perifocal halo nor postcontrast enhancement. In two autoptically proved cases, both chest plain film and CT scans were normal (false negatives). In CI body examinations, were fownd in 6 cases, other sites of organ involvement by Cundidu species (of brain in l/6). Key Worde Computed tomography, Intracranial candidosis, Lung, Fungal disease, Aspergillosis, Lung infection

the beginning of the pulmonary symptoms), middle (n = 5, within 15 days), or late (n = 2, after 15 days). All patients, referred for body CT examination after conventional chest radiographs, had neutropenia and persistent spiking fever despite broad-spectrum antibiotic therapy. When low density lesions in other organs were present, based on the size and number of low density lesions, the abnormalities have been categorized from several (3+) to no lesion (0) (Table 2).

Fungal opportunistic pneumonias are a common source of morbidity and mortality in the immunocompromised host. Neutropenic patients with underlying hematopoietic malignancies are the most common clinical setting (1, 5, 6, 8). The CT features of angioinvasive fungal pneumonias (AFP) have been well described in the last years ( 1, 2), while CT study of pneumonias from Cundidu species has been not so extensively reported. Invasive pulmonary aspergillosis (IPA) is the most common AFP (1,2). MATERIALS

AND

RESULTS

I. AFP

A summary of the typical CT findings in AFP found in our series of 10 patients is presented in Table 1. Two basic types of involvement were observed: (a) multiple nodules with or without one larger, dominant mass (n = 3), or (b) a single masslike infiltrate or nodule (n = 3). In 5 middle or late examinations was found a combination of wedgeshaped consolidation and a or b. A single wedgeshaped consolidation was never found. The single mass-like infiltrates in early scans were surrounded by a halo of low attenuation (Fig. I), in nonenhanced examinations, at lung setting. In 4/8 post-contrast examinations, was observed a rim enhancement in round lesions-either before or after 7 days from the beginning of the clinical setting (Fig. 2). In other 2/S cases was found an incomplete peripheral enhancement. An air bronchogram was evident in wedge shaped consolidations, in 5/5 cases (Fig. 3).

METHODS

A retrospective study of the CT findings in 28 histologically proved fungal opportunistic pneumonias was undertaken. Thirty-two scans were done with (n = 23) or without (n = 15) IV nonionic contrast medium, either on a Somatom DR- 1 equipment or by a Philips Tomoscan 350 scanner (2-5 set, 450 mAs, 125 kVp). Contiguous 1 cm thick sections were obtained. Chest scans were photographed at lung (level = -600/700 H.U. window, width 1000/l 150 H.U.) and soft tissue (level 30/40 H.U., width 500 H.U.) settings. The available CT scans in the AFP have been defined as: early (n = 3, within 7 days from

* Please address correspondence to: G. Potente, Via Severano, 25 00 16 1 Roma-Italy. 423

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Fig. 1. A 12-year-old leukemic girl with invasive pulmonary aspergillosis. CT scan showing a mass-like infiltrate surrounded by a halo of low attenuation at lung setting.

Air crescent sign was observed in 3 nonearly examinations. Brain and body examination in these patients did not show any abnormality compatible with fungal lesions. Table 1. CT findings in Angioinvasive Fungal Pneumonias

Type of involvement A-Multiple nodules with or without one larger, dominant mass B-Wedge shaped consolidation (single) C--Single mass-like/ nodule D-Combination of A and B E-Halo sign F-Cavitation G-Air bronchogram in wedge shaped consolidation *CONTRASTENHANCED H-Peripheral enhancement I-Rim enhancement

(AFP)

CT scans and time early / middle / late / (total) n=3 / n=5 / n=2 / (10)

0

3

0

/

(3)

0

0

0

I

(0)

3

0

0

I

(3)

0 3 0

3 0 2

2 0 1

: I

;:; (3)

0

3

2

I

(5)

N=*3 3 2

/ N=*3 2 1

/ N= *2 / (8110) 1

I

(6) (4)

II. Candida pneumonias In Candida pneumonias (n = 18) were found in chest CT examination: (a) mass-like infiltrate, without Kuhlman’s halo sign ( I), in 6/ 18 cases (Fig. 4). In 4 cases, at mediastinal setting were evident hypodense areas in the infiltrates (not shown), compatible with necrosis. In no one case was found an air crescent formation. In post-contrast examination, peripheral enhancement was always absent; (b) granular pattern (air-space or alveolar disease) in 4/l 8; (c) a mixed or interstitial pattern in other 6 cases. In 2 autoptically proved cases of Candida pneumonia, both chest plain films and CT scans were normal (false negatives). Of the 18 patients with Candida pneumonia, 12 had leukemia as primary disease, 4 lymphomas, 2 other forms of cancer. In 6/18

Table 2. Body and brain CT findings in 6 patients with Candida pneumonia Low density lesions

Liver

(3+) +++ (several large) (2+) ++ (few large) (I+)+ (singlelarge) (0) - (none) Total

1 2 4

Spleen

Kidneys

2

2 2

1 1 5

Brain 1 1

Fungal opportunisticpneumonias 0 G. POTENTE

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On macroscopic examination, the characteristic early lesions of IPA are l-to-3 cm nodules, or “target lesions” (3). These early lesions have a central gray area of necrosis, (infarcted tissue), surrounded by a red peripheral ring from hemorrhagic infarction. A thrombosed artery can be seen at the edge of the lesion. Target lesions arise from transbronchial spread of fungal organisms (Aspergillus or Mucor species) to adjacent pulmonary vessels, with consequent thrombosis and ischemic necrosis of small areas of lung. The hemorrhagic peripheral ring of target lesions has been correlated by Hruban et al. (2) to the halo sign. The rim enhancement feature in our series, similarly, could be correlated to the hemorrhagic ring of target lesions. In our opinion, the halo sign could partly correspond to edema. Perifocal edema is a common finding around infarcted tissue in lung (4). The same CT findings have been caused by mucormycosis and other angiotropic fungi in our series, as expected but not previously described (1). The CT halo sign, therefore, is not specific of IPA, but may be suggestive of angioinvasive pulmonary disease. Little septic emboli

Fig. 2. A 23-year-old woman with AFP. This post-contrast scan, obtained late in the course of infection, shows two distinct types of lesions: a round lesion with rim enhancement, and a large wedge-shaped consolidation with inhomogeneity.

cases, all with mass-like infiltrates in lung examination, were found other sites of fungal involvement, as depicted in the Table 2. In l/6 of these cases was involved the brain (Fig. 5) in 2/6 the kidneys (Fig. 6). In 3 cases, the CT finding was an aspecific hepatomegaly (n = 2) or splenomegaly (n = 1). In the other cases, the livers in 2 patients, spleens in 4 showed few or several lesions in the centimeter range scattered throughout the argans in contrast enhanced scans (Fig. 6). DISCUSSION CT features of Cantfida pneumonia have not been previously describedl, at our knowledge. Kuhlman and other authors (1,2) have assessed the usefulness of CT examinations, when making decisions about the management of opportunistic pneumonias. In their work, the characteristic halo sign in early invasive pulmonary aspergillosis (IPA) has been reported. Hruban et al. (2) have correlated the halo sign to the pathologic findings in one case of IPA.

Fig. 3. Invasive pulmonary mucormycosis. This large air space consolidation was appreciable few days after the beginning of clinical setting. Air bronchogram is well evident.

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Fig. 4. Candida pneumonia. A scan, obtained early in the course of clinical setting of respiratory disease, demonstrating a mass-like infiltrate in the upper right lung. Absence of halo sign and of cavities.

Fig. 5. Precontrast CT axial scan in disseminated candidiasis showing multiple bilateral hypodensities. The ventricules are enlarged.

could cause the same finding, so we are currently investigating about the specificity of round infarction in AFP, to possibly distinguish them from septic infarctions. The transbronchial origin of IPA lesions is the cause of a finding at autopsies, well described by DeGregorio et al. (5): infection with Aspergillus is generally confined to the lung, whereas infection with Candida is widely disseminated. Linker et al. (6) have described, in their series of 20 patients with Candida pneumonias, a multiorgan involvement in 17/20 at autopsy. In their opinion, multiorgan involvement implicates hematogenous dissemination as the most likely avenue of spread. Because the bowel is probably the most frequent portal of entry of Candida, hepatic and splenic enlargement are common (5). This finding in CT examinations has been an aspecific sign of systemic candidiasis in our series. CT finding in hepatosplenic and renal candidiasis has been recently investigated by Shirkhoda (8). CT features of systemic candidiasis are often due to advanced dissemination of fungi, too late for a successful therapy (5). Small microabscesses, however, are susceptible to be treated in the early phases (6,7, 89). In another series of 8 patients, we found in

Fungal opportunistic pneumonias 0 G. POTENTE

Fig. 6. A 59-year-old leukemic patient with autoptically proven systemic candidiasis. Post-contrast scans showed diffuse large hypodensities in spleen, kidneys, and liver.

Fig. 7. A 9-year-old girl with Candida microabscesses, without respiratory symptoms. Numerous lesions in liver are seen on CT post-contrast examination. The size of abscesses varies between 1 and 3 mm.

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CT examination hepatosplenic microabscesses from fungal agents (Candida, n = 7; Trichosporon, n = l), without pneumonia (Fig. 7). Primary disease such as lymphoma (or, very rarely, leukemia) can involve organs and have a CT appearance similar to fungal abscesses. Needle percutaneous biopsy or open-wedge biopsy must be done to confirm the diagnosis and initiate the appropriate therapy (8, 9). SUMMARY Early diagnosis of Aspergillus and similar angioinvasive fungal pneumonias (AFP) is often possible by CT examinations. The characteristic findings in AFP are: 1. One or more nodules or mass-like infiltrates surrounded by a halo of low attenuation at lung setting (halo sign). 2. Peripheral post-contrast enhancement of round lesions at mediastinal setting, with a rim enhancement in 50% of cases. 3. Abnormalities are confined to the thorax. The pattern of widely disseminated large localizations (brain, kidney, liver, spleen) and pulmonary aspecific bilateral opacities or consolidations-without neither halo sign nor peripheral post-contrast enhancement-may indicate systemic candidiasis in a late phase of infection. Low-density microabscesses in the millimeter range in liver, spleen, or kidneys are more frequently found in early systemic candidiasis.

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REFERENCES 1. Kuhlman, J.E.; Fishman, E.K.; Siegelman, S.S. Invasive pulmonary aspergillosis in acute leukemia: characteristic findings on CT, the CT halo sign, and the role of CT in early diagnosis. Radiology 157:611-614; 1985. 2. Hruban, R.H.; Meziane, M.A.; Zerhouni, E.A.; Wheeler, P.S.; Dumler, J.S.; Hutchins, G.M. Radiologic-pathologic correlation of the CT halo sign in invasive pulmonary aspetgillosis. Case report. J. Comput. Assist. Tomogr. 3:534-536; 1987. 3. OK, D.P.; Meyerowitz, R.L.; Dubois, P.J. Pathoradiologic correlation of invasive pulmonary aspergillosis in the compromised host. Cancer 41:2028-2039; 1978. 4. Nordenstrom, B.E.W. Biokinetic impact on structure and imaging of the lung. Am. J. Roentg. 145:447-467; 1985. 5. DeGregorio, M.W.; Lee, W.M.F.; Linker, C.A.; Jacobs, R.A.; Ries, C.A. Fungal infections in patients with acute leukemia. Am. J. Med. 73~543-548; 1982. 6. Linker, CA.; DeGregorio, M.W.; Ries, CA. Computerized tomography in the diagnosis of systemic candidiasis in patients with acute leukemia. Med. Pediatr. Oncol. 12:380-385; 1984. 7. Haron, E.; Feld, R.; Tuffnell, P.; Patterson, B.; Hasselback, R.; Matlow, A. Hepatic candidiasis: an increasing problem in immunocompromised patients. Am. J. Med. 83:17-26; 1987. 8. Shirkoda, A. CT findings in hepatosplenic and renal candidiasis. J. Comput. Assist. Tomogr 11:795-798; 1987. 9. Pastakia, B.; Shawker, T.H.; Thaler, M.; O’Leary, T.; Pizzo, P.A. Hepatosplenic candid&is: wheels within wheels. Radiology 166:417-421; 1988.

About the Author-GIUSEPPE POTENTEreceived his M.D. from the University of Rome “La Sapienza” in 1974. Following residence training in Diagnostic Radiology and Oncologic Radiotherapy at the IRUR (Institute of Radiology, University of Rome), he received his board certificate in 1978. His research and clinical activity center about chest imaging and opportunistic infections in cancer patients. He is currently Assistant Professor of Radiology at the University of Rome “La Sapienza.”