Chest Imaging

Marchiori et al.
CT and Pathologic Findings of Pulmonary Disease in AIDS
Downloaded from www.ajronline.org by 2409:4041:d00:46ae:75e1:af27:e21e:2f26 on 06/12/21 from IP address 2409:4041:d00:46ae:75e1:af27:e21e:2f26. Copyright ARRS. For personal use only; all rights reserved

Pictorial Essay
Pulmonary Disease in Patients with AIDS:
High-Resolution CT and Pathologic Findings
Edson Marchiori1, Nestor L. Müller2, Arthur Soares Souza, Jr.3, Dante Luiz Escuissato4, Emerson Leandro Gasparetto4, Tomás Franquet5
Marchiori E, Müller NL, Souza AS Jr, Escuissato DL, Gasparetto EL, Franquet T

he advent of new prophylactic renchymal complications remain the main The risk of developing specific pulmo-

T and treatment options has re-

sulted in a considerable increase
in the length of survival of HIV-
infected patients. However, pulmonary pa-
cause of morbidity and mortality in these pa-
tients [1]. Early diagnosis and treatment of
these complications are important to im-
nary complications is influenced by the de-
gree of immunosuppression [2]. Patients
with fewer than 500 CD4 cells/mm3 are at
prove survival. increased risk for developing bacterial pneu-

A B

Fig. 1.—32-year-old man with AIDS and Pneumocystis carinii pneumonia.

A, High-resolution CT scan shows bilateral areas of ground-glass attenuation. Note sharp demarcation between abnormal and normal parenchyma and mild smooth thick-
ening of some of interlobular septa.
B, 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)

Received May 4, 2004; accepted after revision July 23, 2004.

1Department of Radiology, Hospital Clementino Fraga, Universidade Federal Fluminense e Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
2Department of Radiology, Vancouver General Hospital, University of British Columbia, 899 W 12th Ave., Vancouver, BC V5Z 1M9, Canada. Address correspondence to N. L. Müller
(nmuller@vanhosp.bc.ca).
3Department of Radiology, Hospital de Base da Faculdade de Medicina (FAMERP) e Instituto de Radiodiagnóstico Rio Preto, São José do Rio Preto, São Paulo, Brazil.
4Department of Diagnostic Radiology, University of Paraná, Curitiba, Brazil.
5Departmento de Radiologia, Hospital de Sant Pau, Avda San Antonio M. Claret 167, Barcelona 08025, Spain.

AJR 2005;184:757–764 0361–803X/05/1843–757 © American Roentgen Ray Society

AJR:184, March 2005 757


Downloaded from www.ajronline.org by 2409:4041:d00:46ae:75e1:af27:e21e:2f26 on 06/12/21 from IP address 2409:4041:d00:46ae:75e1:af27:e21e:2f26. Copyright ARRS. For personal use only; all rights reserved
monia, pulmonary tuberculosis, and lym-
phoproliferative disorders. The risk for these
complications increases further as the pa-
tients 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 pneu-
monia, AIDS-related lymphoma, and Ka-
posi’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. How-
ever, 5–10% of patients with AIDS and pul-
monary disease have normal or nonspecific
radiographic findings [3]. High-resolution
CT is more sensitive than radiography for
revealing parenchymal abnormalities in pa-
tients with AIDS and is superior to radio-
graphy in the differential diagnosis of the
pulmonary complications seen in these pa-
tients [3].
Several studies have shown that the high-
resolution CT findings of pulmonary disease
seen in patients who do not have AIDS reflect
the macroscopic pathologic findings. How-
ever, limited information is available about
the correlation of the high-resolution CT and
pathologic findings in patients with AIDS.
Fig. 2.— 42-year-old woman with AIDS and miliary tuberculosis.
A, High-resolution CT scan shows numerous small nodules in random distribution.
B, Photomicrograph of whole-mount, low-power histologic section reveals multiple granulomas (arrows) with necrotic centers. (H and E, ×40)
758
Marchiori et al.
The aim of this pictorial essay is to illustrate
the high-resolution CT and pathologic find-
ings of the most common pulmonary compli-
cations in patients with AIDS.
P. Carinii Pneumonia
The most common high-resolution CT
manifestation of P. carinii pneumonia con-
sists of patchy or confluent, symmetric, bilat-
eral ground-glass opacities. Less common
manifestations include bilateral areas of con-
solidation, interlobular septal thickening, in-
tralobular 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).
The ground-glass opacities and areas of con-
solidation reflect the presence of alveolar filling
by a foamy exudate, constituted mainly of sur-
factant, 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 opaci-
ties can result from interstitial edema or cellular
infiltration. The nodules reflect the presence of
granulomatous inflammation consisting of clus-
ters of epithelioid histiocytes and multinucle-
ated giant cells [4]. Rarely, granulomas
secondary to P. carinii pneumonia may undergo
necrosis and cavitate.
Cystic lesions are seen on high-resolution
CT in 10–30% of AIDS patients with P. cari-
A B
nii pneumonia. They can reflect the presence
of bullae, intraparenchymal cysts, or, occa-
sionally, necrotizing granulomas. Some of the
cysts have been shown to be secondary to tis-
sue invasion by P. carinii followed by necro-
sis. 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, trac-
tion bronchiectasis, and architectural distor-
tion [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 re-
activation tuberculosis in the normal host. In
these patients, the most common high-resolu-
tion 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 result-
ing in a tree-in-bud pattern. The characteristic
histologic lesion of tuberculosis is a necrotiz-
AJR:184, March 2005
 CT and Pathologic Findings of Pulmonary Disease in AIDS
Downloaded from www.ajronline.org by 2409:4041:d00:46ae:75e1:af27:e21e:2f26 on 06/12/21 from IP address 2409:4041:d00:46ae:75e1:af27:e21e:2f26. Copyright ARRS. For personal use only; all rights reserved

A B

Fig. 3.—44-year-old woman with AIDS and bacterial pneumonia.

A, 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 opac-
ities resulting in tree-in-bud pattern (arrows).
B, 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)

ing granuloma that can expand, resulting in
consolidation and typically cavitation. Endo-
bronchial spread to the bronchioles results in
centrilobular nodular opacities and a tree-in-
bud pattern.
In more severely immunocompromised pa-
tients, the radiologic manifestations tend to re-
semble those of primary disease and consist
predominantly of areas of consolidation, mil-
iary disease (Fig. 2), 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 typi-
cally contain necrotizing granulomas. Up to

A B

Fig. 4.—19-year-old man with AIDS and miliary histoplasmosis.

A, High-resolution CT scan shows numerous small nodules in random distribution.
B, Photomicrograph of histologic section reveals granulomas, some of which are confluent in parenchymal interstitium. (H and E, ×40)

AJR:184, March 2005 759

 Marchiori et al.
Downloaded from www.ajronline.org by 2409:4041:d00:46ae:75e1:af27:e21e:2f26 on 06/12/21 from IP address 2409:4041:d00:46ae:75e1:af27:e21e:2f26. Copyright ARRS. For personal use only; all rights reserved

20% of severely immunocompromised AIDS
patients with pulmonary tuberculosis have ra-
diographs that show normal findings [2]. High-
resolution CT in these patients usually shows
small nodules and lymph node enlargement [2].
Bacterial Pneumonia
The imaging findings of bacterial pneu-
monia in patients with AIDS are similar to
those observed in immunocompetent patients
and consist predominantly of single or multi-
focal areas of consolidation [2]. Lobar pneu-
monia 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 charac-
terized by centrilobular inflammation that is
concentrated around respiratory bronchioles
(Fig. 3), with spread to the surrounding alve-
olar ducts and alveolar spaces. Bronchopneu-
monia can result from a variety of gram-
positive and gram-negative bacteria, most
commonly those in the Staphylococcus, Strep-
tococcus, Pseudomonas, Klebsiella, Entero-
bacter, and Haemophilus genera.
Histoplasmosis and Coccidioidomycosis
Patients with AIDS who are exposed to his-
toplasmosis and coccidioidomycosis are at in-
creased risk of developing disseminated
disease. The high-resolution CT findings con-
sist of a miliary pattern (Fig. 4A), or, less com-
monly, diffuse air-space consolidation [4]. The
miliary lesions result from hematogenous dis-
semination and consist of small foci of acute in-

A B

C D

Fig. 5.—62-year-old man with AIDS and invasive pulmonary aspergillosis.

A, High-resolution CT scan obtained at level of upper lobes shows nodule with surrounding halo of ground-glass attenuation (arrows) in right upper lobe.
B, 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.
C, 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)
D, 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)

760 AJR:184, March 2005

 CT and Pathologic Findings of Pulmonary Disease in AIDS
Downloaded from www.ajronline.org by 2409:4041:d00:46ae:75e1:af27:e21e:2f26 on 06/12/21 from IP address 2409:4041:d00:46ae:75e1:af27:e21e:2f26. Copyright ARRS. For personal use only; all rights reserved

A B

Fig. 6.—37-year-old man with AIDS and cryptococcal infection.

A, High-resolution CT scan shows numerous small nodules in random distribution, characteristic of miliary disease.
B, Photomicrograph of histologic section shows one of the nodules (arrow). (H and E, ×40).

flammation with neutrophils, macrophages, and
granulomas. Diffuse air-space consolidation is
typically associated with large numbers of or-
ganisms in the alveoli and an inflammatory re-
sponse consisting of neutrophils with a mixture
of fibrin, RBCs, and macrophages.
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 his-
tologic abnormalities consist of tissue inva-
sion, abscess formation, and angioinvasion
with or without infarction. The cavitary le-
sions reflect the presence of pulmonary in-
farction and abscess formation [6]. Less
common CT findings include single or multi-
ple nodules, patchy areas of consolidation,
and pleural effusions [6]. The nodules may
have a surrounding halo of ground-glass at-
tenuation. The nodules reflect the presence of
infarction and histologically display coagu-
lating necrosis and fungus hyphae; the halo is
due to surrounding hemorrhage (Fig. 5).
Cryptococcosis
Cryptococcosis in patients with AIDS usually
manifests as disseminated disease, the main clin-
ical manifestation being meningitis. The pulmo-
nary 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 granu-
lomas similar to those seen in other fungal pul-
monary infections [4] (Fig. 6B). In severely
immunosuppressed patients, there may be exten-
sive tissue infiltration by organisms in a pneu-
monic fashion, with little tissue response.
Cytomegalovirus Pneumonia
Cytomegalovirus is commonly detected on
bronchoalveolar lavage fluid in AIDS pa-
tients. In most cases, it is an incidental find-
ing, there being no associated pulmonary
complication. In a small number of patients,
however, Cytomegalovirus organisms can re-
sult in disseminated infection and pneumonia.
The high-resolution CT findings are hetero-
geneous and include bilateral ground-glass
opacities, patchy bilateral consolidation, and
multiple nodules or masslike areas of consol-
idation [1] (Fig. 7).
Kaposi’s Sarcoma
The characteristic high-resolution CT mani-
festations of Kaposi’s sarcoma consist of peri-
bronchovascular interstitial thickening and
irregular or ill-defined nodules in a predomi-
nantly peribronchovascular distribution (Fig. 8).
These findings reflect the propensity of Ka-

Fig. 7.—38-year-old man with AIDS and Cytomegalovirus pneumonia. High-resolu-

tion CT scan shows bilateral nodules (straight arrows), focal ground-glass opacities
(curved arrows), and consolidation (arrowhead).

AJR:184, March 2005 761

 Marchiori et al.
Downloaded from www.ajronline.org by 2409:4041:d00:46ae:75e1:af27:e21e:2f26 on 06/12/21 from IP address 2409:4041:d00:46ae:75e1:af27:e21e:2f26. Copyright ARRS. For personal use only; all rights reserved

posi’s sarcoma cells to infiltrate predominately
the perihilar peribronchovascular interstitium
[7] (Fig. 8). Other common findings include
thickening of the interlobular septa, lymphade-
nopathy, and pleural effusion. The interlobular
septal thickening can result from infiltration by
tumor cells or edema (Fig. 8).
Lymphoma
AIDS-related lymphoma is typically a
high-grade B-cell non-Hodgkin’s lymphoma.
It most commonly originates in extranodal lo-
cations in the lungs, bone marrow, central ner-
vous system, and bowel.
The most common pulmonary manifestation
consists of multiple nodules or masses measur-
ing 1–5 cm in diameter. The nodules reflect the
presence of a dense focal monomorphic cellular
infiltrate. Less common findings include local-
ized or multiple areas of consolidation, interlob-
ular 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 peri-
bronchovascular 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 inter-
lobular septa and the pleural surface reflects the
presence of infiltration of these regions by tu-
mor cells [8].

A B

C D

Fig. 8.—34-year-old man with AIDS and Kaposi’s sarcoma.

A, High-resolution CT scan shows marked peribronchial thickening, perivascular nodularity (straight arrows), nodules along interlobar fissures (curved arrows), and thick-
ening of interlobular septa.
B, High-resolution CT scan obtained at more caudal level than A shows extensive interlobular septal thickening and centrilobular nodules (arrows).
C, Photomicrograph of histologic specimen shows edema and tumor cells, which produce thickening of interlobular septa (arrows). (H and E, ×40)
D, 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)

762 AJR:184, March 2005

 CT and Pathologic Findings of Pulmonary Disease in AIDS
Downloaded from www.ajronline.org by 2409:4041:d00:46ae:75e1:af27:e21e:2f26 on 06/12/21 from IP address 2409:4041:d00:46ae:75e1:af27:e21e:2f26. Copyright ARRS. For personal use only; all rights reserved

A B

Fig. 9.—52-year-old man with AIDS and non-Hodgkin’s lymphoma.

A, High-resolution CT scan shows bilateral consolidation in predominantly peribronchial distribution, nodule in lingula (straight arrow), and few centrilobular nodules (curved arrows).
B, 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 lym-
phoproliferative 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 manifes-
tations consist of poorly defined bilateral centri-
lobular nodules, smooth or nodular thickening
of the bronchovascular bundles, and ground-
glass opacities [2] (Fig. 10A). Histologically,
lymphocytic interstitial pneumonia is character-
ized by an interstitial infiltrate of lymphocytes
and plasma cells that involves the perilymphatic
interstitium along the bronchovascular bundles,
resulting in bronchial wall thickening and cen-
trilobular nodules (Fig. 10B). Interlobular septal
thickening and small subpleural nodules are
also commonly present. The cellular infiltrate
typically extends diffusely along the alveolar

A B

Fig. 10.—24-year-old woman with AIDS and lymphocytic interstitial pneumonia.

A, 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).
B, 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)

AJR:184, March 2005 763


Downloaded from www.ajronline.org by 2409:4041:d00:46ae:75e1:af27:e21e:2f26 on 06/12/21 from IP address 2409:4041:d00:46ae:75e1:af27:e21e:2f26. Copyright ARRS. For personal use only; all rights reserved
Fig. 11.—7-year-old boy with AIDS and nonspecific interstitial pneumonia. High-resolution CT scan shows patchy bilat-
eral ground-glass opacities, small foci of consolidation, and poorly defined centrilobular nodular opacities (arrows).
septa, resulting in ground-glass opacities visible
on high-resolution CT [4, 8].
Nonspecific Interstitial Pneumonia
Nonspecific interstitial pneumonia is a rela-
tively common abnormality in patients with AIDS
characterized histologically by mild to moderate
lymphocytic and plasma cell infiltration of the
peribronchiolar, perivascular, and interlobular sep-
764
Marchiori et al.
good prognosis, typically stabilizing or resolving
spontaneously or with treatment.
References
tal 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 pa-
tients with CD4 cell counts of less than 200 cells/
mm3 [2]. Nonspecific interstitial pneumonia has a
1. McGuinness G. Changing trends in the pulmo-
nary manifestations of AIDS. Radiol Clin North
Am 1997;35:1029–1082
2. Boiselle PM, Aviram G, Fishman JE. Update on lung
disease in AIDS. Semin Roentgenol 2002;37:54–71
3. Kang EY, Staples CA, McGuinness G, Primack
SL, Müller NL. Detection and differential diagno-
sis of pulmonary infections and tumors in patients
with AIDS: value of chest radiography versus CT.
AJR 1996;166:15–19
4. Travis WD, Colby TV, Koss MN, Rosado-de-
Christensen ML, Müller NL, King TE Jr. Non-
neoplastic disorders of the lower respiratory
tract: atlas of nontumor pathology. Washington,
DC: Armed Forces Institute of Pathology, 2002
5. Laissy JP, Cadi M, Boudiaf ZE, et al. Pulmonary
tuberculosis: computed tomography and high-res-
olution computed tomography patterns in patients
who are either HIV-negative or HIV-seropositive.
J Thorac Imaging 1998;13:58–64
6. 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
7. Traill ZC, Miller RF, Shaw PJ. CT appearances of
intrathoracic Kaposi’s sarcoma in patients with
AIDS. Br J Radiol 1996;69:1104–1107
8. Katzenstein ALA. Katzenstein and Askin’s surgi-
cal pathology of non-neoplastic lung disease, 3rd
ed. Philadelphia, PA: Saunders, 1997
AJR:184, March 2005