Pictorial Essay
Chest Imaging
March 2005

Pulmonary Disease in Patients with AIDS: High-Resolution CT and Pathologic Findings

The advent of new prophylactic and treatment options has resulted in a considerable increase in the length of survival of HIV-infected patients. However, pulmonary parenchymal complications remain the main cause of morbidity and mortality in these patients [1]. Early diagnosis and treatment of these complications are important to improve survival.
The risk of developing specific pulmonary complications is influenced by the degree of immunosuppression [2]. Patients with fewer than 500 CD4 cells/mm3 are at increased risk for developing bacterial pneumonia, pulmonary tuberculosis, and lymphoproliferative disorders. The risk for these complications increases further as the patients become more immunocompromised. When the CD4 cell count falls below 200 cells/mm3, the patients are also at increased risk for developing Pneumocystis carinii pneumonia and disseminated tuberculosis. Fungal infections, Cytomegalovirus pneumonia, AIDS-related lymphoma, and Kaposi's sarcoma usually occur in severely immunocompromised patients (< 100 CD4 cells/mm3) [2].
In most patients with AIDS, a confident diagnosis of the pulmonary complications can be made by a combination of clinical, radiographic, and laboratory findings. However, 5–10% of patients with AIDS and pulmonary disease have normal or nonspecific radiographic findings [3]. High-resolution CT is more sensitive than radiography for revealing parenchymal abnormalities in patients with AIDS and is superior to radiography in the differential diagnosis of the pulmonary complications seen in these patients [3].
Several studies have shown that the highresolution CT findings of pulmonary disease seen in patients who do not have AIDS reflect the macroscopic pathologic findings. However, limited information is available about the correlation of the high-resolution CT and pathologic findings in patients with AIDS. The aim of this pictorial essay is to illustrate the high-resolution CT and pathologic findings of the most common pulmonary complications in patients with AIDS.

P. Carinii Pneumonia

The most common high-resolution CT manifestation of P. carinii pneumonia consists of patchy or confluent, symmetric, bilateral ground-glass opacities. Less common manifestations include bilateral areas of consolidation, interlobular septal thickening, intralobular linear opacities, cystic lesions, and nodules [1, 3]. The combination of ground-glass opacities and superimposed intralobular linear opacities results in a pattern commonly referred to as crazy paving (Fig. 1A).
Fig. 1A. —32-year-old man with AIDS and Pneumocystis carinii pneumonia. High-resolution CT scan shows bilateral areas of ground-glass attenuation. Note sharp demarcation between abnormal and normal parenchyma and mild smooth thickening of some of interlobular septa.
The ground-glass opacities and areas of consolidation reflect the presence of alveolar filling by a foamy exudate, constituted mainly of surfactant, fibrin, and cellular debris [1] (Fig. 1B). The organisms are typically seen within this foamy exudate as small bubbles [4]. Interlobular septal thickening and intralobular linear opacities can result from interstitial edema or cellular infiltration. The nodules reflect the presence of granulomatous inflammation consisting of clusters of epithelioid histiocytes and multinucleated giant cells [4]. Rarely, granulomas secondary to P. carinii pneumonia may undergo necrosis and cavitate.
Fig. 1B. —32-year-old man with AIDS and Pneumocystis carinii pneumonia. Photomicrograph of histologic specimen shows septal thickening (straight arrows) secondary to edema and cellular inflammatory infiltrates separating two secondary lobules. Note partial filling of air spaces by inflammatory infiltrate (curved arrows), which accounts for ground-glass opacities seen on CT scan (A). (H and E, ×40)
Cystic lesions are seen on high-resolution CT in 10–30% of AIDS patients with P. carinii pneumonia. They can reflect the presence of bullae, intraparenchymal cysts, or, occasionally, necrotizing granulomas. Some of the cysts have been shown to be secondary to tissue invasion by P. carinii followed by necrosis. The cysts are usually bilateral and involve mainly the upper lobes. Patients with cysts have an increased propensity to develop pneumothorax [4].
Occasionally, P. carinii pneumonia may result in interstitial fibrosis that can be mild or severe. The fibrosis is manifested on CT by the presence of irregular linear opacities, traction bronchiectasis, and architectural distortion [1, 4].

Tuberculosis

Patients with AIDS are at increased risk of developing tuberculosis. The manifestations of tuberculosis in HIV-positive patients are influenced by the degree of cellular immune compromise [5]. In patients who have CD4 cell counts greater than 200 cells/mm3, the findings tend to be similar to those seen in reactivation tuberculosis in the normal host. In these patients, the most common high-resolution CT manifestations consist of a single or, less commonly, multiple 1- to 3-cm-diameter nodules; consolidation; cavitation involving mainly the upper lobes; and centrilobular nodular and branching linear opacities resulting in a tree-in-bud pattern. The characteristic histologic lesion of tuberculosis is a necrotizing granuloma that can expand, resulting in consolidation and typically cavitation. Endobronchial spread to the bronchioles results in centrilobular nodular opacities and a tree-in-bud pattern.
In more severely immunocompromised patients, the radiologic manifestations tend to resemble those of primary disease and consist predominantly of areas of consolidation, miliary disease (Figs. 2A and 2B), pleural effusion, and lymph node enlargement [4, 5]. Lymph node enlargement results from inflammation of the lymphatic vessels within the nodes and of the nodes themselves. The enlarged nodes typically contain necrotizing granulomas. Up to 20% of severely immunocompromised AIDS patients with pulmonary tuberculosis have radiographs that show normal findings [2]. High-resolution CT in these patients usually shows small nodules and lymph node enlargement [2].
Fig. 2A. — 42-year-old woman with AIDS and miliary tuberculosis. High-resolution CT scan shows numerous small nodules in random distribution.
Fig. 2B. — 42-year-old woman with AIDS and miliary tuberculosis. Photomicrograph of whole-mount, low-power histologic section reveals multiple granulomas (arrows) with necrotic centers. (H and E, ×40)

Bacterial Pneumonia

The imaging findings of bacterial pneumonia in patients with AIDS are similar to those observed in immunocompetent patients and consist predominantly of single or multifocal areas of consolidation [2]. Lobar pneumonia is characterized by the spread of bacteria and inflammatory exudates between the alveolar air spaces, a pattern seen most commonly in Streptococcus pneumoniae pneumonia. A lobular distribution is characterized by centrilobular inflammation that is concentrated around respiratory bronchioles (Figs. 3A and 3B), with spread to the surrounding alveolar ducts and alveolar spaces. Bronchopneumonia can result from a variety of grampositive and gram-negative bacteria, most commonly those in the Staphylococcus, Streptococcus, Pseudomonas, Klebsiella, Enterobacter, and Haemophilus genera.
Fig. 3A. —44-year-old woman with AIDS and bacterial pneumonia. High-resolution CT scan shows foci of air-space consolidation with adjacent ground-glass attenuation in dorsal lung regions. Also note branching linear and nodular opacities resulting in tree-in-bud pattern (arrows).
Fig. 3B. —44-year-old woman with AIDS and bacterial pneumonia. Photomicrograph of histologic specimen shows bronchiolar bifurcation with inflammatory infiltrate in lumen (straight arrow) and in peribronchiolar region (curved arrows), corresponding to tree-in-bud pattern shown on high-resolution CT. (H and E, ×40)

Histoplasmosis and Coccidioidomycosis

Patients with AIDS who are exposed to histoplasmosis and coccidioidomycosis are at increased risk of developing disseminated disease. The high-resolution CT findings consist of a miliary pattern (Fig. 4A), or, less commonly, diffuse air-space consolidation [4]. The miliary lesions result from hematogenous dissemination and consist of small foci of acute inflammation with neutrophils, macrophages, and granulomas. Diffuse air-space consolidation is typically associated with large numbers of organisms in the alveoli and an inflammatory response consisting of neutrophils with a mixture of fibrin, RBCs, and macrophages.
Fig. 4A. —19-year-old man with AIDS and miliary histoplasmosis. High-resolution CT scan shows numerous small nodules in random distribution.
Fig. 4B. —19-year-old man with AIDS and miliary histoplasmosis. Photomicrograph of histologic section reveals granulomas, some of which are confluent in parenchymal interstitium. (H and E, ×40)

Invasive Pulmonary Aspergillosis

The most common high-resolution CT finding of invasive pulmonary aspergillosis in patients with AIDS is the presence of thick-walled cavitary lesions. The predominant histologic abnormalities consist of tissue invasion, abscess formation, and angioinvasion with or without infarction. The cavitary lesions reflect the presence of pulmonary infarction and abscess formation [6]. Less common CT findings include single or multiple nodules, patchy areas of consolidation, and pleural effusions [6]. The nodules may have a surrounding halo of ground-glass attenuation. The nodules reflect the presence of infarction and histologically display coagulating necrosis and fungus hyphae; the halo is due to surrounding hemorrhage (Figs. 5A, 5B, 5C, and 5D).
Fig. 5A. —62-year-old man with AIDS and invasive pulmonary aspergillosis. High-resolution CT scan obtained at level of upper lobes shows nodule with surrounding halo of ground-glass attenuation (arrows) in right upper lobe.
Fig. 5B. —62-year-old man with AIDS and invasive pulmonary aspergillosis. High-resolution CT scan obtained at level of middle and lower lobes shows small nodules in lingula and left lower lobe (arrows) and localized scarring in right lower lobe.
Fig. 5C. —62-year-old man with AIDS and invasive pulmonary aspergillosis. Photomicrograph of histologic specimen of one of small nodules shows necrotic center (straight arrows) surrounded by leukocytic infiltrate (curved arrows) and more peripherally by alveolar hemorrhage (arrowheads). (H and E, ×40)
Fig. 5D. —62-year-old man with AIDS and invasive pulmonary aspergillosis. On photomicrograph of histologic specimen, black of Grocott-Gomori methenamine–silver nitrate stain reveals hyphae of Aspergillus organisms with radial distribution inside nodule from center to periphery. (×40)

Cryptococcosis

Cryptococcosis in patients with AIDS usually manifests as disseminated disease, the main clinical manifestation being meningitis. The pulmonary manifestations are variable and include bilateral nodular or reticular opacities, bilateral consolidation, or miliary nodules [1] (Fig. 6A). The histologic response to cryptococcal infection depends on the immune status of the patient. In patients with normal or nearly normal immune response, the organisms result in nodular granulomas similar to those seen in other fungal pulmonary infections [4] (Fig. 6B). In severely immunosuppressed patients, there may be extensive tissue infiltration by organisms in a pneumonic fashion, with little tissue response.
Fig. 6A. —37-year-old man with AIDS and cryptococcal infection. High-resolution CT scan shows numerous small nodules in random distribution, characteristic of miliary disease.
Fig. 6B. —37-year-old man with AIDS and cryptococcal infection. Photomicrograph of histologic section shows one of the nodules (arrow). (H and E, ×40).

Cytomegalovirus Pneumonia

Cytomegalovirus is commonly detected on bronchoalveolar lavage fluid in AIDS patients. In most cases, it is an incidental finding, there being no associated pulmonary complication. In a small number of patients, however, Cytomegalovirus organisms can result in disseminated infection and pneumonia. The high-resolution CT findings are heterogeneous and include bilateral ground-glass opacities, patchy bilateral consolidation, and multiple nodules or masslike areas of consolidation [1] (Fig. 7).
Fig. 7. —38-year-old man with AIDS and Cytomegalovirus pneumonia. High-resolution CT scan shows bilateral nodules (straight arrows), focal ground-glass opacities (curved arrows), and consolidation (arrowhead).

Kaposi's Sarcoma

The characteristic high-resolution CT manifestations of Kaposi's sarcoma consist of peribronchovascular interstitial thickening and irregular or ill-defined nodules in a predominantly peribronchovascular distribution (Figs. 8A, 8B, 8C, and 8D). These findings reflect the propensity of Kaposi's sarcoma cells to infiltrate predominately the perihilar peribronchovascular interstitium [7] (Figs. 8A, 8B, 8C, and 8D). Other common findings include thickening of the interlobular septa, lymphadenopathy, and pleural effusion. The interlobular septal thickening can result from infiltration by tumor cells or edema (Figs. 8A, 8B, 8C, and 8D).
Fig. 8A. —34-year-old man with AIDS and Kaposi's sarcoma. High-resolution CT scan shows marked peribronchial thickening, perivascular nodularity (straight arrows), nodules along interlobar fissures (curved arrows), and thickening of interlobular septa.
Fig. 8B. —34-year-old man with AIDS and Kaposi's sarcoma. High-resolution CT scan obtained at more caudal level than A shows extensive interlobular septal thickening and centrilobular nodules (arrows).
Fig. 8C. —34-year-old man with AIDS and Kaposi's sarcoma. Photomicrograph of histologic specimen shows edema and tumor cells, which produce thickening of interlobular septa (arrows). (H and E, ×40)
Fig. 8D. —34-year-old man with AIDS and Kaposi's sarcoma. Photomicrograph of histologic specimen shows tumor cells infiltrating peribronchiolar connective tissue, which results in centrilobular nodules seen on high-resolution CT. (H and E, ×40)

Lymphoma

AIDS-related lymphoma is typically a high-grade B-cell non-Hodgkin's lymphoma. It most commonly originates in extranodal locations in the lungs, bone marrow, central nervous system, and bowel.
The most common pulmonary manifestation consists of multiple nodules or masses measuring 1–5 cm in diameter. The nodules reflect the presence of a dense focal monomorphic cellular infiltrate. Less common findings include localized or multiple areas of consolidation, interlobular septal thickening, centrilobular nodules, and, occasionally, reticular infiltrates that may have a peribronchovascular distribution (Fig. 9A). The air-space consolidation results from the filling of the alveoli by tumor cells. The peribronchovascular thickening is secondary to the infiltration of the peribronchovascular bundles by neoplastic cells. Extension to the interstitium along the bronchioles results in centrilobular nodules (Fig. 9B). The thickening of the interlobular septa and the pleural surface reflects the presence of infiltration of these regions by tumor cells [8].
Fig. 9A. —52-year-old man with AIDS and non-Hodgkin's lymphoma. High-resolution CT scan shows bilateral consolidation in predominantly peribronchial distribution, nodule in lingula (straight arrow), and few centrilobular nodules (curved arrows).
Fig. 9B. —52-year-old man with AIDS and non-Hodgkin's lymphoma. Photomicrograph of histologic section shows infiltration around bronchiole and arteriole by tumor cells. Such infiltration results in centrilobular nodular opacities seen on high-resolution CT. (H and E, ×40)

Lymphocytic Interstitial Pneumonia

Lymphocytic interstitial pneumonia is a lymphoproliferative disorder seen with increased frequency in patients with AIDS, particularly children. In most of these patients, the disorder is benign and regresses spontaneously or with treatment. Rarely, it evolves into lymphoma [4]. The most common high-resolution CT manifestations consist of poorly defined bilateral centrilobular nodules, smooth or nodular thickening of the bronchovascular bundles, and ground-glass opacities [2] (Fig. 10A). Histologically, lymphocytic interstitial pneumonia is characterized by an interstitial infiltrate of lymphocytes and plasma cells that involves the perilymphatic interstitium along the bronchovascular bundles, resulting in bronchial wall thickening and centrilobular nodules (Fig. 10B). Interlobular septal thickening and small subpleural nodules are also commonly present. The cellular infiltrate typically extends diffusely along the alveolar septa, resulting in ground-glass opacities visible on high-resolution CT [4, 8].
Fig. 10A. —24-year-old woman with AIDS and lymphocytic interstitial pneumonia. High-resolution CT scan shows patchy bilateral ground-glass opacities, small foci of consolidation, mild septal thickening (straight arrows), and few small nodules (curved arrows).
Fig. 10B. —24-year-old woman with AIDS and lymphocytic interstitial pneumonia. Photomicrograph of histologic specimen shows lymphocyte aggregates resulting in nodular appearance (straight arrows). In some areas, lesions are abundant (curved arrows) and result in collapse of alveolar spaces, which results in ground-glass opacities and air-space consolidation seen on high-resolution CT. (H and E, ×40)

Nonspecific Interstitial Pneumonia

Nonspecific interstitial pneumonia is a relatively common abnormality in patients with AIDS characterized histologically by mild to moderate lymphocytic and plasma cell infiltration of the peribronchiolar, perivascular, and interlobular septal interstitial tissue [2]. It is distinguished from lymphocytic interstitial pneumonia by the lack of involvement of the alveolar interstitium [2, 4]. The clinical and radiologic findings mimic those of P. carinii pneumonia (Fig. 11). However, nonspecific interstitial pneumonia typically is seen early in AIDS patients with normal CD4 cell counts, whereas P. carinii pneumonia occurs mainly in patients with CD4 cell counts of less than 200 cells/mm3 [2]. Nonspecific interstitial pneumonia has a good prognosis, typically stabilizing or resolving spontaneously or with treatment.
Fig. 11. —7-year-old boy with AIDS and nonspecific interstitial pneumonia. High-resolution CT scan shows patchy bilateral ground-glass opacities, small foci of consolidation, and poorly defined centrilobular nodular opacities (arrows).

Footnote

Address correspondence to N. L. Müller ([email protected]).

References

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McGuinness G. Changing trends in the pulmonary manifestations of AIDS. Radiol Clin North Am 1997; 35:1029-1082
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Boiselle PM, Aviram G, Fishman JE. Update on lung disease in AIDS. Semin Roentgenol 2002; 37:54-71
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Kang EY, Staples CA, McGuinness G, Primack SL, Müller NL. Detection and differential diagnosis of pulmonary infections and tumors in patients with AIDS: value of chest radiography versus CT. AJR 1996; 166:15-19
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Travis WD, Colby TV, Koss MN, Rosado-de-Christensen ML, Müller NL, King TE Jr. Nonneoplastic disorders of the lower respiratory tract: atlas of nontumor pathology. Washington, DC: Armed Forces Institute of Pathology, 2002
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Laissy JP, Cadi M, Boudiaf ZE, et al. Pulmonary tuberculosis: computed tomography and high-resolution computed tomography patterns in patients who are either HIV-negative or HIV-seropositive. J Thorac Imaging 1998; 13:58-64
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Staples CA, Kang EY, Wright JL, Phillips P, Müller NL. Invasive pulmonary aspergillosis in AIDS: radiographic, CT, and pathologic findings. Radiology 1995; 196:409-414
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Traill ZC, Miller RF, Shaw PJ. CT appearances of intrathoracic Kaposi's sarcoma in patients with AIDS. Br J Radiol 1996; 69:1104-1107
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Information & Authors

Information

Published In

American Journal of Roentgenology
Pages: 757 - 764
PubMed: 15728594

History

Submitted: May 4, 2004
Accepted: July 23, 2004

Authors

Affiliations

Edson Marchiori
Department of Radiology, Hospital Clementino Fraga, Universidade Federal Fluminense e Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Nestor L. Müller
Department of Radiology, Vancouver General Hospital, University of British Columbia, 899 W 12th Ave., Vancouver, BC V5Z 1M9, Canada.
Arthur Soares Souza, Jr.
Department of Radiology, Hospital de Base da Faculdade de Medicina (FAMERP) e Instituto de Radiodiagnóstico Rio Preto, São José do Rio Preto, São Paulo, Brazil.
Dante Luiz Escuissato
Department of Diagnostic Radiology, University of Paraná, Curitiba, Brazil.
Emerson Leandro Gasparetto
Department of Diagnostic Radiology, University of Paraná, Curitiba, Brazil.
Tomás Franquet
Departmento de Radiologia, Hospital de Sant Pau, Avda San Antonio M. Claret 167, Barcelona 08025, Spain.

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