AJR 2005; 184:273-282
© American Roentgen Ray Society
Diffuse High-Attenuation Pulmonary Abnormalities: A Pattern-Oriented Diagnostic Approach on High-Resolution CT
Edson Marchiori1,
Arthur S. Souza, Jr.2,
Tomás Franquet3 and
Nestor L. Müller3
1 Department of Radiology, Universidade Federal Fluminense and Hospital
Universitario Clementino Fraga Filho, Rio de Janeiro, Brazil.
2 Department of Radiology, Faculdade de Medicina (FAMERP) e Ultra X, São
José do Rio Preto, SP, Brazil.
3 Department of Radiology, Vancouver Hospital and Health Sciences Center and
University of British Columbia, 855 W 12th Ave., Vancouver, BC V5Z 1M9,
Canada.
Received March 1, 2004;
accepted after revision June 30, 2004.
Address correspondence to N. L. Müller.
Introduction
Diffuse high-attenuation pulmonary abnormalities can result from the
deposition of calcium or, less commonly, other high-attenuation material such
as talc, amiodarone, iron, mercury, and barium sulfate
[1]. Deposition of calcium
salts in tissues or ossification can be secondary to calcification in a
collagen matrix (bone tissue) with or without marrow elements
[2].
High-resolution CT is highly sensitive in the detection of areas of
abnormally high attenuation in the lung parenchyma, blood vessels, and
airways. However, limited information is available on the high-resolution CT
findings of diffuse high-attenuation pulmonary abnormalities and the role of
CT in the differential diagnosis.
The aim of this pictorial essay is to present a classification scheme of
the various entities that can result in diffuse high-attenuation pulmonary
abnormalities based on the pattern and distribution of findings on
high-resolution CT. The findings can be classified into five main patterns:
diffuse small calcified nodules, diffuse small high-attenuation noncalcified
nodules, multiple calcified large nodules or masses, high-attenuation linear
or reticular pattern, and high-attenuation consolidation. A better
understanding of the different conditions associated with high attenuation in
the lungs allows a more confident and specific diagnosis.
Diffuse Small Calcified Nodules
Small calcified nodules refer to nodular opacities measuring less than 10
mm in diameter that have focal of diffuse calcification evident on
high-resolution CT. Small calcified nodules most commonly are secondary to
dystrophic calcification in previously damaged lung parenchyma. Causes of
small calcified nodules distributed diffusely throughout the lung parenchyma
include infections, pulmonary metastases, chronic hemorrhagic conditions,
occupational diseases, deposition diseases, and idiopathic disorders such as
pulmonary alveolar microlithiasis.
Infections
Small calcified parenchymal nodules most commonly are a result of
dystrophic calcification in areas of injured lung
[1]. Dystrophic calcification
follows caseation, necrosis, or fibrosis. Postinfectious calcified nodules are
well circumscribed and measure 2-5 mm in diameter
(Fig. 1). These nodules can be
seen commonly in patients with healed disseminated histoplasmosis and rarely
as a sequela of miliary tuberculosis. Most patients with multiple pulmonary
nodular calcifications secondary to tuberculosis or histoplasmosis have
calcified hilar or mediastinal lymph nodes (or both)
[1,
2]. Late development of tiny
widespread micronodular calcification with nodules 1-3 mm in diameter through
both lungs is an uncommon sequela of varicella (chickenpox) pneumonia (Figs.
2A and
2B). There is no associated
calcification of lymph nodes.
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Fig. 1. —Residual postprimary pulmonary tuberculosis in 56-year-old
man. High-resolution CT scan obtained using tissue window settings at level of
aortic arch shows mediastinal left pleural thickening and multiple calcified
granulomatous lesions (arrow).
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Fig. 2A. —62-year-old woman with residual varicella infection.
High-resolution CT scan at level of inferior pulmonary veins shows numerous
bilateral small nodules. Nodules (arrows) are smoothly marginated and
sharply defined.
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Fig. 2B. —62-year-old woman with residual varicella infection. CT scan
obtained with soft-tissue window settings at approximately same level as
A clearly shows that many nodules (arrows) are calcified.
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Metastatic Pulmonary Calcifications
Metastatic calcification of the pulmonary parenchyma is associated with a
variety of benign and malignant disorders such as primary and secondary
hyperparathyroidism, chronic renal failure, sarcoidosis, IV calcium therapy,
multiple myeloma, and massive osteolysis caused by metastases
[1,
2]. In patients with chronic
renal failure, high-resolution CT shows multiple 3- to 10-mm calcified nodules
or, more commonly, fluffy nodular opacities that mimic air-space nodules but
that contain foci of calcification (Fig.
3A). Metastatic pulmonary calcification typically is most marked
in the upper lobes [2]. This
distribution results from the relatively alkaline environment in the upper
lobes due to the considerably greater high ventilation-perfusion ratios as
compared with the lower lung zones
[2]. A frequent associated
finding is calcification in the vessels of the chest wall
(Fig. 3B).
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Fig. 3A. —54-year-old woman with chronic renal failure. High-resolution
CT scan through lung apices shows diffuse bilateral and confluent fluffy
high-attenuation centrilobular nodules (arrows) involving upper
lobes. Note that nodules are a few milimeters away from pleura, a
characteristic finding of centrilobular nodules.
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Chronic Hemorrhagic Conditions (Hemosiderosis)
Idiopathic pulmonary hemosiderosis is an uncommon cause of alveolar
hemorrhage that occurs predominantly in infants and young adults. Recurrent
episodes of alveolar hemorrhage over several years are characteristic of this
entity. With recurrent hemorrhage, patients develop pulmonary hemosiderosis
that results in dense centrilobular nodular opacities on high-resolution CT.
This distribution presumably is secondary to predominately peribronchiolar
accumulation of hemosiderin and fibrosis
(Fig. 4). In patients with
severe hemosiderosis, calcium often is added to the hemosiderin deposits
attracting foreign-body giant cells, a process that has been termed
"endogenous pneumoconiosis." Secondary hemosiderosis due to mitral
stenosis also may present with small multifocal calcified nodules.
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Fig. 4. —30-year-old woman with idiopathic pulmonary hemosiderosis.
High-resolution CT scan shows extensive bilateral centrilobular ground-glass
opacities and both poorly defined and well-defined centrilobular nodules. Some
nodules have increased attenuation, but no calcification is evident on CT.
Patient had repeated episodes of diffuse pulmonary hemorrhage since early
childhood. High-resolution CT findings had not changed appreciably over
several years.
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Occupational Diseases
Diffuse calcified small nodules, often associated with egg-shell
calcification of hilar or mediastinal lymph nodes, can occur in silicosis and
coal workers' pneumoconiosis (Figs.
5A and
5B). Whereas silicosis is
caused by inhalation of free silica during occupational exposure such as
mining and sandblasting, coal workers' pneumoconiosis results from inhalation
of coal dust after exposure to washed coal
[2]. High-resolution CT
findings of silicosis and coal workers' pneumoconiosis include diffuse and
randomly distributed small well-defined nodules that are most prominent in the
middle and upper lung zones
[1]. The nodules usually
measure less than 5 mm in diameter and may calcify.
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Fig. 5A. —Silicosis in 50-year-old man. High-resolution CT scan
obtained using soft-tissue window settings shows conglomerate mass of fibrosis
containing multiple calcified small nodules. Also note characteristic
peripheral "egg-shell" calcification of mediastinal nodes
(arrows).
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Fig. 5B. —Silicosis in 50-year-old man. High-resolution CT scan
obtained using soft-tissue window settings shows bilateral areas of irregular
parenchymal bands and architectural distortion (arrows). Numerous
well-defined small calcified nodules are seen bilaterally with sparing of lung
periphery.
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Calcified nodules also can be seen in the accumulation in lung macrophages
of iron oxide (siderosis), tin oxide (stannosis), and barium dust (baritosis).
Stannosis is a condition in which tin oxide is deposited in lung tissue after
inhalation. Tin oxide is radiologically visible, although there is no tissue
reaction to its presence [1,
2] (Figs.
6A and
6B). Baritosis is one of the
benign types of pneumoconiosis in which inhaled particulate matter lies in the
lungs for years without producing symptoms, interference with lung function,
or liability to develop pulmonary or bronchial infections or other thoracic
disease. Owing to the high radiopacity of barium, the discrete shadows on
chest radiography are extremely dense
[1,
2].
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Fig. 6B. —Stannosis in 48-year-old man. High-resolution CT scan
obtained using lung window settings at level of carina shows small calcified
nodules. Nodules are sharply defined. Conglomeration of nodules is present in
right upper lobe. Calcified mediastinal nodes also are visible.
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Pulmonary Alveolar Microlithiasis
Pulmonary alveolar microlithiasis is a rare pulmonary disorder of unknown
cause characterized by the intraalveolar development and accumulation of
spherical microliths of calcium phosphate
[1]. This disorder may be
detected incidentally on chest radiographs obtained for other reasons. The
characteristic radiographic and high-resolution CT findings consist of
innumerable tiny sandlike calcified micronodules distributed bilaterally
throughout both lungs [3]
(Figs. 7A and
7B). Other findings include
calcified interlobular septa and small subpleural cysts. The apparent
calcification of septa on CT is due to accumulation of calcospherites in
alveoli adjacent to the septa
[3].
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Fig. 7A. —Pulmonary alveolar microlithiasis in 35-year-old woman.
(Courtesy of Ravin C, Durham, NC.) High-resolution CT scan obtained using lung
window settings shows diffuse scattered micronodules (arrows) through
both lungs. There is confluence of nodules in dependent lung regions.
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Fig. 7B. —Pulmonary alveolar microlithiasis in 35-year-old woman.
(Courtesy of Ravin C, Durham, NC.) High-resolution CT scan obtained at same
level as A using soft-tissue window settings shows numerous dense
calcific areas of attenuation in dependent lung regions and calcific
thickening of interlobular septa (arrows).
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Diffuse Small High-Attenuation Noncalcified Nodules
Talcosis
Talc (magnesium silicate) acts as a filler and lubricant in tablets
containing oral medications. Talcosis is seen in drug users who inject
medications intended for oral use
[4]. Once crushed, dissolved,
and IV injected, numerous talc particles become trapped within pulmonary
arterioles and capillaries. Pathologically, talcosis consists of multiple
small granulomas composed of multinucleated cells containing birefringent
crystals. The initial high-resolution CT findings consist of numerous
high-attenuation nodules measuring less than 1 mm in diameter or diffuse
ground-glass opacities [4].
Over time the nodules can become confluent and result in high-attenuation
confluent masses (Figs. 8A and
8B). The high attenuation
results from talc deposition within the pulmonary arterioles, capillaries, and
interstitium.
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Fig. 8A. —Talcosis in 26-year-old female IV drug user. High-resolution
CT scan obtained using lung window settings shows conglomerated masses in
upper lobes. Note diffuse fine granular and linear pattern surrounding
conglomerate masses.
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Fig. 8B. —Talcosis in 26-year-old female IV drug user. CT scan obtained
using soft-tissue window settings shows highly attenuated material within
masses (arrows), a finding that suggests talc deposition.
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Mercury and Acrylic Cement Embolism
IV mercury injection is infrequent and mostly is related to suicide
attempts and iatrogenic injections from metallic mercury used as an anaerobic
seal on blood gas-sampling syringes. The characteristic radiographic and
high-resolution CT findings consist of multiple small metallic spherules
diffusely scattered throughout both lungs
[1]. Additional metallic
deposits are visible in the heart, abdominal vessels, or extremities. The
metallic densities often can persist for years.
Pulmonary embolism caused by acrylic cement is a rare complication
associated with vertebroplasty. CT manifestations consist of multiple
radiopaque tubular areas of increased density corresponding to emboli in the
segmental and subsegmental levels of the pulmonary arteries
[5]
(Fig. 9). CT also may depict
perivertebral leaks.
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Fig. 9. —Polymethyl methacrylate embolism in 56-year-old woman after
undergoing percutaneous vertebroplasty. Unenhanced CT scan shows radiopaque
emboli in superior vena cava (arrowhead) and in segmental and
subsegmental levels of pulmonary arteries (arrow). (Courtesy of
Verschakelen J, Leuven, Belgium)
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Multiple Large Calcified Nodules or Masses
Large calcified nodules refer to nodular areas measuring 10-30 mm in
diameter, and calcified masses refer to round or oval areas measuring greater
than 30 mm in diameter that have focal or diffuse calcification evident on
high-resolution CT. The main diagnostic considerations are calcified pulmonary
metastases, amyloidosis, calcified hyalinizing granulomas, necrobiotic
nodules, and progressive massive fibrosis
[1,
2]. The triad of
gastrointestinal stromal tumors, extraadrenal paraganglioma, and multiple
pulmonary chondromas (Carney's triad) is a rare chronic, persistent, and
indolent disease of unknown cause primarily affecting women
[6]. Calcification of pulmonary
chondromas is a common radiologic finding (Figs.
10A and
10B).
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Fig. 10A. —Multiple pulmonary chondromas in 43-year-old woman with
gastrointestinal stromal tumor. Contrast-enhanced CT scan of upper abdomen
shows large heterogeneous lobulated mass arising from stomach
(arrows). Cystic component of mass and multiple intratumoral
low-attenuation areas of necrosis (arrowheads) also are seen.
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Fig. 10B. —Multiple pulmonary chondromas in 43-year-old woman with
gastrointestinal stromal tumor. Chest CT scan obtained using mediastinal
window settings shows multiple pulmonary calcified chondromas of different
sizes. (Courtesy of Llauger J, Barcelona, Spain)
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Calcified Pulmonary Metastases
Calcification in pulmonary metastases is very uncommon and can result from
either sarcomas (osteosarcomas, chondrosarcomas, synovial sarcomas, and giant
cell tumors of the bone) or carcinomas (mucin-producing carcinomas,
adenocarcinomas, thyroid malignancies, and treated metastatic
choriocarcinomas) [7]
(Fig. 11). Several mechanisms
are responsible for calcification in metastases: bone formation in tumor
osteoid in an osteosarcoma; calcification and ossification of tumor cartilage
in a chondrosarcoma; dystrophic calcification in a papillary carcinoma of the
thyroid, giant cell tumor of the bone, synovial sarcoma, or treated metastatic
tumor; and mucoid calcification in a mucinous adenocarcinoma of the
gastrointestinal tract and breast
[1,
7]. The high-resolution CT
findings consist of solitary or multiple calcified nodules with well-defined
margins. Although calcification usually is invisible on chest radiographs, it
may be identifiable radiologically when there is sufficient calcium
deposition.
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Fig. 11. —Multiple pulmonary metastases from osteosarcoma in
24-year-old man. Unenhanced CT scan obtained using mediastinal window settings
shows multiple calcified pulmonary metastases and large paraspinal partially
calcified mass (arrow), adjacent to thoracic aorta.
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Amyloidosis
Primary amyloidosis results from the abnormal production and excessive
deposition of amyloid light chain protein secreted by B lymphocytes and plasma
cells. Pathologically, respiratory involvement occurs in 50% of patients with
amyloidosis. Pulmonary amyloid infiltration results in either localized or
diffuse pulmonary disease [8].
Pulmonary amyloidosis may appear in three major forms: tracheobronchial,
nodular, and diffuse parenchymal. The high-resolution CT findings of the
diffuse parenchymal form include small well-defined nodules (2-4 mm in
diameter), abnormal reticular opacities, interlobular septal thickening, and
subpleural confluent consolidations
[8]. The nodular form shows
solitary or multiple nodules of well-defined rounded or lobular borders.
Approximately 50% of nodules calcify or ossify (Figs.
12A and
12B).
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Fig. 12A. —Nodular parenchymal amyloidosis in asymptomatic 48-year-old
man. CT scan obtained using lung window settings shows multiple, bilateral,
and randomly distributed pulmonary nodules. They range in diameter from 0.2 to
4 cm.
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Fig. 12B. —Nodular parenchymal amyloidosis in asymptomatic 48-year-old
man. CT scan obtained at different level than A using mediastinal
window settings shows that many nodules are calcified. Note small calcified
nodules in subpleural location.
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Hyalinizing Granulomas
Hyalinizing granuloma is a rare condition of unknown etiology. Possibly a
chronic immune reaction to endogenous or exogenous antigens or infectious
agents such as Histoplasma capsulatum or Mycobacterium organisms, it
occurs in an individual predisposed to marked scar formation
[1]. Histologically, the center
of the lesion consists of hyaline collagen arranged in a distinctive pattern
of concentric lamellae sometimes with focal calcification or ossification.
Pulmonary hyalinizing granuloma manifests radiologically as solitary or
multiple nodules with well-defined borders, ranging in size from a few
millimeters to 15 cm in diameter
[1,
2] (Figs.
13A and
13B). Cavitation is
unusual.
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Fig. 13A. —Multiple pulmonary hyalinizing granulomas in asymptomatic
56-year-old man. Chest CT scan obtained using lung window settings shows
multiple circumscribed nodules and masses of different sizes.
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Fig. 13B. —Multiple pulmonary hyalinizing granulomas in asymptomatic
56-year-old man. CT scan corresponding to A obtained using mediastinal
window settings shows that many nodules are calcified irregularly.
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Progressive Massive Fibrosis
The most prominent CT feature of progressive massive fibrosis associated
with either silicosis or coal workers' pneumoconiosis is masslike
consolidation (conglomerate masses) associated with parenchymal scarring and
adjacent bullae (cicatricial emphysema), usually in the upper lobes
[1,
2]. Conglomerate masses usually
are oval and have irregular borders. Although usually bilateral, unilateral
conglomerate masses may occur and be confused with carcinoma. Progressive
massive fibrosis always is associated with a background of small nodules
visible on high-resolution CT. Punctate calcification in association with
conglomerate masses is common (Figs.
14A and
14B).
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Fig. 14A. —Progressive massive fibrosis due to silicosis in 57-year-old
man. High-resolution CT scan obtained using lung window settings shows
bilateral conglomerate masses. Irregular linear opacities and distortion of
lung architecture (arrows), indicative of fibrosis, are evident.
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Fig. 14B. —Progressive massive fibrosis due to silicosis in 57-year-old
man. CT scan obtained using soft-tissue window settings at same level as
A shows areas of punctate calcification within conglomerate masses.
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Linear or Reticular Pattern: Disseminated Pulmonary Ossification
Disseminated pulmonary ossification can be idiopathic or associated with a
variety of pulmonary, cardiac, and systemic disorders. The interstitial
dystrophic pulmonary ossification can be localized or distributed widely.
Dendriform pulmonary ossification, defined as widespread heterotopic bone
formation within the lungs, is an infrequent form of diffuse pulmonary
ossification [2]. Usually
unrecognized radiographically while the patient is alive, it typically is
diagnosed at postmortem examination. In chronic pulmonary fibrosis, branching
spicules of bone extend through the lung interstitium in a racemose or
dendriform manner [9] (Figs.
15A and
15B). Although such
calcification often is invisible on chest radiographs, high-resolution CT
performed using the appropriate window settings shows tiny calcific opacities
in the periphery of the lung
[1,
2].
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Fig. 15A. —80-year-old man with idiopathic pulmonary fibrosis.
High-resolution CT scan obtained through lower lung zones shows bilateral fine
reticular opacities in subpleural lung regions (arrow).
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Fig. 15B. —80-year-old man with idiopathic pulmonary fibrosis. CT scan
obtained corresponding to A using mediastinal window settings reveals
multiple punctuate calcifications (arrows) within these opacities,
representing dendritic calcification.
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High-Attenuation Consolidation
Amiodarone Lung
Deposition of iodine can occur within the lung parenchyma as a result of
treatment with amiodarone, a triiodinated antiarrhythmic drug
[10]. Approximately 6% of
individuals receiving amiodarone develop pulmonary toxicity. Discontinuation
of therapy typically is associated with a good prognosis. The most common CT
findings include septal thickening and interstitial fibrosis. Amiodarone
pulmonary toxicity can result in high-attenuation focal or multifocal
parenchymal opacities due to incorporation of amiodarone into the type II
pneumocytes [10]
(Fig. 16). These opacities
usually are peripheral in location.
Iodinated Oil Embolism
Iatrogenic causes of iodinated oil embolism occur either after
transcatheter oil chemoembolization (Fig.
17) or after lymphangiography. High-resolution CT findings consist
of multifocal patchy areas of ground-glass attenuation and high-attenuation
areas of consolidation and collapse
[11].
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Fig. 17. —Oil embolism after chemoembolization of right hepatic lobe
for hepatocellular carcinoma in 46-year-old woman. Unenhanced CT scan obtained
1 day after chemoembolization shows bilateral deposition of ethiodized oil in
lower lobes. Bilateral pleural effusion is present also.
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Pulmonary Alveolar Microlithiasis
The characteristic high-resolution CT findings consist of innumerable
bilateral, calcified micronodules measuring less than 1 mm in diameter. In
patients with long-standing disease, the numerous adjacent nodules result in
areas of consolidation on CT
[3] (Figs.
7A and
7B).
Conclusion
High-attenuation pulmonary abnormalities can result from a variety of
different conditions. We have presented a diagnostic approach based on the
presence and distribution of five main patterns of disease on high-resolution
CT: diffuse small calcified nodules, diffuse small high-attenuation
noncalcified nodules, multiple calcified large nodules or masses,
high-attenuation linear or reticular pattern, and high-attenuation
consolidation.
Small calcified nodules most commonly are seen in patients with previous
infection, particularly tuberculosis and histoplasmosis, and in patients with
silicosis or coal workers' pneumoconiosis. Less common causes include
metastatic pulmonary calcifications, pulmonary metastases, hemosiderosis, and
alveolar microlithiasis.
Small high-attenuation noncalcified nodules most commonly are seen in
patients with talcosis due to IV drug use. Occasionally these nodules may
result from IV injection of mercury or may be iatrogenic secondary to
pulmonary embolism of acrylic cement. Large calcified masses most often are
seen in association with progressive massive fibrosis in silicosis and in
conglomeration of talc granulomas. Less commonly they are due to calcified
pulmonary metastases. Other causes such as amyloidosis and hyalinizing
granulomas are rare. High-attenuation consolidation is seen in amiodarone lung
and, less commonly, in iodinated oil embolism and pulmonary alveolar
microlithiasis. Linear or reticular calcification is rare.
Differential diagnosis is based on the five main patterns of abnormalities:
in their distribution in the lungs and in the presence of associated findings
such as calcified hilar and mediastinal nodes. However, the proposed
diagnostic algorithm has limitations. For example, the pattern of diffuse
small nodules in patients with alveolar microlithiasis may resemble the
pattern of talcosis seen in patients who are IV drug users. Furthermore,
several conditions may result in more than one pattern. For example, both
talcosis and silicosis may result in high-attenuation conglomerated masses of
fibrosis.
Despite these limitations, we believe that the proposed diagnostic approach
can be helpful in the differential diagnosis of the various conditions that
result in high attenuation of the pulmonary parenchyma.
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Introduction
Diffuse Small Calcified Nodules
