10 

10

Pneumoconioses
Kelly J. Butnor, MD, and Victor L. Roggli, MD

important determinants of fibrosis. For example, crystalline silica is

Overview and General Considerations  335 highly fibrogenic, whereas carbon is an innocuous nuisance dust. Host
Types of Pneumoconiosis  335 factors include the efficiency of clearance mechanisms and individual
Silicosis 335 susceptibility. Many of the dusts have a characteristic reaction pattern
Coal Workers’ Pneumoconiosis  339 or appearance in histologic sections, which permits an accurate diagnosis
Asbestosis 342 (Table 10.1). The silicotic nodule and the asbestos body are familiar
Silicatosis (Silicate Pneumoconiosis)  347 examples. Others are associated with a reaction pattern that may suggest
Talcosis (Talc Pneumoconiosis)  349 the diagnosis, but a careful occupational history or use of supplemental
Siderosis 351 analytic techniques may be required to confirm the diagnosis, as with
Aluminosis 353 berylliosis, in which the histologic findings closely resemble those in
Hard Metal Lung Disease  354 sarcoidosis.
Berylliosis 356 Analytic electron microscopy provides a powerful tool for identifying
Rare Earth Pneumoconiosis  358 dusts in lung tissue samples, and these methods are emphasized when
Other Pneumoconioses  358 appropriate.2 An analytic electron microscope consists of a scanning
References 361 or transmission electron microscope equipped with an energy-dispersive
spectrometer. Electron microscopic techniques may permit the detection
of particles too small to be observed by light microscopy. Furthermore,
energy-dispersive x-ray analysis (EDXA) identifies the elemental
composition of individual particulates, which can be critical to the
identification and, in some cases, the source of the inhaled dust. It must
Overview and General Considerations be emphasized, however, that the identification of a particular xenobiotic
Pneumoconiosis literally means “dust in the lung,” and the term in lung tissue is in and of itself not proof of disease and must be correlated
has come to refer to disease of the lung related to the inhalation of with the pathologic response (if any) to the dust in routine histologic
dusts. Pneumoconioses are for the most part due to the inhalation sections.
of inorganic dusts in the workplace, and the reaction of the lungs to
these dusts is generally fibrosis. These diseases typically evolve over Types of Pneumoconiosis
several decades, although there are some exceptions to this rule. The Silicosis
pathologic findings in these conditions can resemble those in other Silicosis results from the inhalation of particles of crystalline silica. It
fibrotic and granulomatous disorders of the lung, so the pathologist is characterized by circumscribed areas of nodular fibrosis that tend to
must be familiar with their diagnostic features. Although no specific have the greatest profusion in the upper lung zones. Occupations with
treatment is available for most of these disorders, proper diagnosis is exposure to crystalline silica are summarized in Box 10.1.3 In the past,
crucial for accurate determination of prognosis and, when indicated, very heavy exposures occurred from sandblasting. This type of exposure
compensation. has been banned in most countries but continues in certain parts of
The toxicity and corresponding fibrogenicity of inorganic particulates the world, such as Bangladesh, where sandblasting of denim jeans is
are related to both the nature of the dust and the nature of the host still an industry.4–6 Soil in the extreme eastern and western portions of
response.1 One important feature of particle toxicity is the aerodynamic the United States is rich in alpha quartz (the most common form of
diameter, with particles in the size range of 1 to 5 µm having the highest crystalline silica). Silicotic nodules may be found in the thoracic lymph
probability of deposition and retention within the respiratory tract. In nodes and even within the lung parenchyma in farmers and agricultural
addition, the total inhaled dose and intrinsic properties of the dust are laborers working in these regions.

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Table 10.1  Histopathologic Patterns of Pneumoconioses
Pattern Type Pneumoconiosis/Exposure

Acute lung injury Cadmium

Alveolar filling Pulmonary alveolar Silicosis

proteinosis Aluminosis
Indium
Macrophages/giant cells Hard metal lung disease

Nodules Fibrotic Silicosis

Coal workers’ pneumoconiosis
Silicatosis/mixed dust pneumoconiosis
Silicon carbide (carborundum)
Vineyard sprayer’s lung
With nonnecrotizing Aluminosis
granulomas Berylliosis

Cellular infiltrates With granulomas Vineyard sprayer’s lung Figure 10.1  Silicosis. In this gross specimen, circumscribed areas of nodular fibrosis
With lymphoid hyperplasia ± Flock worker’s lung are slate gray and of firm consistency.
bronchiolitis

Fibrosis With variable involvement Conglomerate silicosis

Coal workers’ pneumoconiosis
(progressive massive fibrosis)
Asbestosis
Silicatosis/mixed dust pneumoconiosis
Talcosis
Aluminosis
Hard metal lung disease
Rare earth pneumoconiosis
Silicon carbide (carborundum)
Dental technician’s pneumoconiosis
Domestically acquired particulate
lung disease
With granulomas Aluminosis
Berylliosis
Rare earth pneumoconiosis

Minimal changes With small airways disease Flavorings-related lung disease Figure 10.2  Silicosis. At low magnification, silicotic nodules are sharply circumscribed
and densely collagenous (Masson trichrome stain).

Box 10.1  Occupations With Exposure to Crystalline Silica the nodules may become confluent (Figs. 10.3 and 10.4). Areas of
Abrasive powder manufacture confluent fibrosis greater than 2 cm in maximum dimension are the
Boiler scaling defining feature of conglomerate silicosis. Cavitation may occur within
Farming* areas of confluent fibrosis and, when present, suggests the possibility
Firebrick manufacture of superimposed tuberculosis.
Foundry work The histologic hallmark of silicosis is the silicotic nodule.7,8 This
Mining (coal, copper, gold, graphite, lead, mica, and tin) lesion is a sharply circumscribed nodule consisting of dense, whorled,
Molding and grinding hyalinized collagen (Figs. 10.5 and eSlide 10.1). More loosely arranged
Pottery and ceramic manufacture collagen bundles are typically found at the periphery of the nodule. In
Quarry work
recently formed lesions, macrophages form a mantle around the fibrotic
Sandblasting, including denim
Stonemasonry
center. Long-standing lesions may be calcified or even ossified (Fig.
Engineered stone countertop fabrication/installation 10.6). The nodules may be present anywhere within the lung parenchyma
but typically are most numerous in the upper lung zones. Not uncom-
*Soil in extreme eastern and western portions of the United States. monly, they are concentrated beneath the pleura (Fig. 10.7). There may
also be extensive pleural fibrosis (Fig. 10.8).9 Nodules are frequently
also present within hilar lymph nodes (Fig. 10.9). In patients with
Clinical Presentation extremely high exposures to very fine silica particles, the pattern of
Patients demonstrate a range of clinical presentations, from asymptomatic resultant lung injury may closely resemble that in pulmonary alveolar
with simple silicosis to markedly dyspneic with conglomerate silicosis. proteinosis, characterized by the presence of granular eosinophilic
In conglomerate silicosis, hypoxemia and cor pulmonale may be fatal. material filling the alveoli, alveolar ducts, and bronchioles (Fig. 10.10).
Cholesterol clefts may be prominent within the intraalveolar material.
Pathologic Findings The granular proteinaceous exudate typically stains strongly positive
Silicotic nodules are of firm consistency and typically slate gray in with periodic acid–Schiff with diastase.
appearance, measuring from a few millimeters to approximately 1 cm Examination with polarizing microscopy shows faintly birefringent
in diameter (Figs. 10.1 and 10.2). As the disease progresses in severity, particulates within the fibrotic nodules (Fig. 10.11). Larger, brightly

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10

Figure 10.5  Silicosis. This silicotic nodule demonstrates the typical whorled appearance.
Macrophages are present at the periphery of the nodule.

Figure 10.3  Conglomerate silicosis. A Gough-Wentworth section of lung from a tobacco

field worker demonstrates confluent fibrosis in the upper lobe (arrowhead).

Figure 10.6  Silicosis. A mature silicotic nodule exhibits partial ossification.

Figure 10.4  Conglomerate silicosis. Multiple silicotic nodules have coalesced, forming
an area of confluent fibrosis.

birefringent particles, which represent silicates, may also be seen, but

these should not predominate (see later section on silicatosis).10 On
scanning electron microscopy the particles appear angulated (Fig. 10.12).
Analytic electron microscopy with EDXA reveals peaks for silicon only
(Fig. 10.13).
Figure 10.7  Silicosis. The lung parenchyma underlying the pleura is a common location
Differential Diagnosis for silicotic nodules.
Silicotic nodules must be distinguished from the fibrotic nodules of
healed or burned-out sarcoidosis, as well as healed mycobacterial or
fungal infections, a classic example being the so-called histoplasmoma. an infectious etiology. Patients with silicosis are at increased risk for
The presence of multinucleated giant cells and the absence of significant acquiring tuberculosis.11 Both processes may be present simultaneously.
dust deposits favor sarcoidosis. Sarcoid granulomas may contain fine Concurrent tuberculosis infection is most likely to occur with conglomer-
needle–like or large, platy birefringent particles, which represent ate silicosis. The occasionally somewhat stellate appearance of the
endogenous calcium carbonate or oxalate, respectively (Fig. 10.14). These macrophage mantle in recently formed silicotic nodules may simulate
particles should not be confused with the foreign material of pneumo- Langerhans cell histiocytosis, but the latter does not contain whorled
coniosis. The presence of necrosis in association with giant cells favors collagen.

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A
Figure 10.9  Silicosis. Silicotic nodules within a lymph node characteristically contain
centrally dense, hyalinized collagen surrounded by concentric whorls of more loosely
arranged collagen bundles.

B
Figure 10.8  Pleural silicosis. (A) Pleural involvement sometimes manifests as dense
fibrosis. (B) At higher magnification, a cellular area consisting of fibroblasts and histiocytes
is evident. Polarizing microscopy showed numerous birefringent particulates.

Figure 10.10  Acute silicosis. Granular eosinophilic material fills alveoli, imparting an
appearance similar to that seen in pulmonary alveolar proteinosis. Note the presence
of a silicotic nodule at left. (From Sporn TA, Roggli VL. Pneumoconioses, mineral and
vegetable. In: Tomashefski JF, ed. Dail and Hammar’s Pulmonary Pathology. Vol 1. 3rd
ed. New York: Springer-Verlag; 2008:911–949, with permission.)

Figure 10.11  Silicosis. Partial polarization of a silicotic nodule demonstrates faintly Figure 10.12  Silicosis. Scanning electron microscopy demonstrates angulated silica
birefringent silica particles. particles.

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10

Figure 10.13  Energy-dispersive x-ray analysis spectrum shows a peak for silicon (Si).
Figure 10.15  Normal lung. A Gough-Wentworth section of normal lung shows scattered
minimal accumulations of anthracotic pigment and intact parenchyma. (From Kleinerman
J, Green FHY, Laquer W, et al. Pathology standards for coal workers pneumoconiosis.
Arch Pathol Lab Med. 1979;103:375–432, with permission.)

to greater amounts of silica than those working at the coal face. Dust
suppression measures greatly reduce the incidence of progressive massive
fibrosis (PMF), the advanced form of CWP.

Clinical Presentation
Patients exhibit a range of clinical presentations, from asymptomatic
with simple CWP to markedly dyspneic with PMF. The latter is associated
with hypoxemia and cor pulmonale and may be fatal.14,15

Pathologic Findings
CWP is characterized by increased pigmentation in the lungs resulting
Figure 10.14  Birefringent particles in sarcoidosis. In contrast to silicosis, this example from the deposition of coal dust (Figs. 10.15–10.17). Foci of accentuated
of sarcoidosis contains large platy birefringent particles, typical of endogenous calcium pigmentation, superimposed on a background of diffusely increased
oxalate. pigment, are present on the pleura and within the lung parenchyma.
In some cases, palpable nodules are present within the lung parenchyma
and usually are most numerous in the upper lung zones. These nodules
Rheumatoid pneumoconiosis, eponymously termed Caplan syndrome, are grossly similar to silicotic nodules except for being black rather
which was originally described in coal miners with rheumatoid arthritis than slate gray (Fig. 10.18). The most advanced cases of CWP feature
but can also be seen in individuals exposed to silica or silicates, reflects greater than 2 cm in maximal dimension confluent areas of irregular
the presence of rheumatoid nodules in association with pneumoconiosis.12 fibrosis with the consistency of vulcanized rubber, typically in the upper
The nodules demonstrate central necrobiosis with peripheral palisading to middle lung zones (Fig. 10.19). These are the lesions of PMF. Cavitation
histiocytes often associated with a rim of dust. may occur in areas of PMF and, when present, suggests superimposed
Extrathoracic location does not rule out a silicotic origin of a fibrous tuberculosis.16
nodule, because silicotic nodules have been found in the liver, spleen, The histologic hallmark of CWP is the coal dust macule (Fig. 10.20).
bone marrow, and abdominal lymph nodes.13 Extrathoracic involvement, Coal dust macules consist of discrete collections of interstitial pigment
when present, usually occurs in the setting of advanced pulmonary deposition in the vicinity of respiratory bronchioles. Areas of emphy-
silicosis. The diagnostic yield of transbronchial biopsy in silicosis is sematous destruction, referred to as focal emphysema, are typically
low, probably because the firm circumscribed nodules are pushed aside present at the periphery of macules. Pigment-laden macrophages may
by the biopsy forceps. be present within alveolar spaces, and pigment deposits may occur
anywhere along the lymphatic routes of the lung including the secondary
Coal Workers’ Pneumoconiosis lobular septa, as well as in the pleura. Lymph nodes frequently contain
Coal workers’ pneumoconiosis (CWP), also known as black lung disease, numerous pigmented macrophages and may also demonstrate silicotic
occurs in persons involved in the mining of coal. The nature of the nodules. Silicotic nodules may also be present within the lung paren-
disease is related to the intensity and duration of exposure, host factors, chyma, but unlike cases of pure silicosis, a collarette of pigmented
and the specific duties of the miner. Workers involved with drilling in macrophages often surrounds the nodules, imparting a “Medusa head”
the ceiling of the shaft or constructing communicating shafts are exposed appearance (Fig. 10.21). Areas of massive fibrosis (Fig. 10.22) consist

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Figure 10.16  Simple coal workers’ pneumoconiosis. This thin section of lung demonstrates Figure 10.17  Simple coal workers’ pneumoconiosis. In contrast to the normal lung,
multiple small, circumscribed black nodules, predominantly in the upper lobe. (From this thin section shows diffusely increased pigment resulting from the deposition of coal
Kleinerman J, Green FHY, Laquer W, et al. Pathology standards for coal workers pneu- dust. (From Kleinerman J, Green FHY, Laquer W, et al. Pathology standards for coal
moconiosis. Arch Pathol Lab Med. 1979;103:375–432, with permission.) workers pneumoconiosis. Arch Pathol Lab Med. 1979;103:375–432, with
permission.)

Figure 10.18  Simple coal workers’ pneumoconiosis. In addition to diffusely increased

pigmentation, the lung parenchyma shows well-demarcated black nodules. Centrilobular
emphysematous bullae are also present.

Figure 10.19  Complicated coal workers’ pneumoconiosis. The upper lobe contains a
confluent irregular area of fibrosis with the consistency of vulcanized rubber. Central
cavitation is present.

Figure 10.20  Simple coal workers’ pneumoconiosis. The coal dust macule is characterized
340
by focal interstitial pigment deposition. In this example, destruction of the adjacent
alveolar septa, termed focal emphysema, is also seen.
 Pneumoconioses

10

Figure 10.23  Complicated coal workers’ pneumoconiosis. In this example of progressive

massive fibrosis, haphazardly arranged collagen bundles are interspersed with abundant
pigment.

Figure 10.21  Simple coal workers’ pneumoconiosis. A collarette of pigmented mac-

rophages gives a “Medusa head” appearance to this intraparenchymal silicotic nodule.

Figure 10.24  Complicated coal workers’ pneumoconiosis. A Masson trichrome stain

highlights the collagenous composition of a heavily pigmented region of progressive
massive fibrosis.

Figure 10.22  Complicated coal workers’ pneumoconiosis. A large, black, irregular

fibrotic lesion has destroyed the perihilar lung parenchyma. (From Kleinerman J, Green
FHY, Laquer W, et al. Pathology standards for coal workers pneumoconiosis. Arch Pathol
Lab Med. 1979;103:375–432, with permission.)

of collagen bundles that are arranged in a haphazard distribution and

intermixed with abundant pigment (Figs. 10.23 and 10.24). Vascular Figure 10.25  Coal workers’ pneumoconiosis. Partial polarization shows a mixture of
faintly and brightly birefringent particles superimposed on black pigment.
obliteration is common within areas of PMF, and ischemia may be the
cause of cavitation in some cases.
Examination with polarizing microscopy typically shows numerous nodules and is an important factor in the pathogenesis of PMF.17 Fer-
faintly to brightly birefringent particulates within a background of black ruginous bodies are sometimes seen in the lungs of coal workers, typically
pigment (Fig. 10.25). This appearance reflects the mixed nature of coal within the alveolar spaces (Fig. 10.26). These may be distinguished
dust, which is composed of amorphous carbon, silicates, and silica. The from true asbestos bodies by virtue of their black carbonaceous cores
presence of silica in coal dust is responsible for the formation of silicotic (Fig. 10.27).18 Tuberculosis may also complicate CWP (Fig. 10.28).

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Figure 10.29  Graphite worker’s pneumoconiosis. Although somewhat similar in

Figure 10.26  Coal workers’ pneumoconiosis. Along with pigmented macrophages, appearance to particulates in coal workers’ pneumoconiosis, graphite particles appear
this case demonstrates numerous intraalveolar ferruginous bodies. crystalline and elicit a giant cell reaction.

Differential Diagnosis
CWP must be distinguished from the anthracotic pigment deposition
that occurs in urban dwellers and cigarette smokers and from graphite
worker’s pneumoconiosis. The extent of pigmentation in normal persons
is a function of environmental exposure to carbon-containing dust and
the natural ability of the lung to rid itself of particulates. Distinction
from CWP is somewhat a matter of degree, but the presence of true
coal dust macules, as described earlier, is indicative of CWP. The finding
of anthracotic pigment-laden macrophages within alveoli is also a useful
feature, but such macrophages may be absent in miners who have been
retired for many years. Graphite worker’s pneumoconiosis appears similar
to CWP, but graphite is crystalline, whereas the carbon present in coal
is amorphous (Fig. 10.29). A giant cell reaction to the crystalline carbon
of graphite assists in this distinction. Transbronchial biopsy may be
useful in the diagnosis of CWP, showing the typical changes described
earlier. However, areas of nodular fibrosis or PMF may be missed by
such sampling. Therefore transbronchial biopsy is not useful for assessing
disease severity.

Figure 10.27  Coal workers’ pneumoconiosis. At higher magnification, the black car-
Asbestosis
bonaceous core of this ferruginous body (pseudoasbestos body) is evident. Asbestosis is defined as pulmonary interstitial fibrosis caused by the
inhalation of asbestos fibers.19 Substantial and significant exposures to
asbestos can occur in a variety of occupational settings, including the
mining and milling of asbestos, the manufacture of asbestos-containing
products, and the use of products containing asbestos. Workers who
may be involved in the use of asbestos-containing products include
insulators, shipyard workers, railroad workers, power plant workers,
US Navy or Merchant Marine seamen, oil or chemical refinery workers,
construction workers, steel and other molten metal workers, and paper
mill workers (Box 10.2). A few cases of asbestosis have also occurred
among household contacts of asbestos workers, apparently as a conse-
quence of exposure to asbestos brought home on the workers’
clothing.

Clinical Presentation
In patients with asbestosis, the clinical presentation ranges from
asymptomatic to severely dyspneic at rest. Hypoxemia and cor pulmonale
may prove fatal in these patients. Pulmonary function testing typically
shows restrictive changes, and the diffusion capacity is reduced. Patients
Figure 10.28  Coal workers’ pneumoconiosis. A caseous granuloma in this case of with asbestosis who smoke cigarettes have a markedly increased risk
coal workers’ pneumoconiosis was found to contain acid-fast bacilli.
for developing lung cancer. Pleural plaques in and of themselves are
rarely symptomatic and, when present in isolation, should not be referred
to as asbestosis. Although the pleural and parenchymal changes caused

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Box 10.2  Industries/Industrial Facilities With Exposure to Asbestos Box 10.3  Histologic Grading of Severity of Fibrosis in Asbestosis*

Asbestos mining and milling Grade 0: No appreciable peribronchiolar fibrosis or fibrosis confined to the bronchiolar 10
Asbestos products manufacture walls
Construction Grade 1: Fibrosis confined to the walls of respiratory bronchioles and the first tier
Glass and ceramic manufacture of adjacent alveoli
Insulation Grade 2: Extension of fibrosis to involve alveolar ducts and/or ≥2 tiers of alveoli
Oil or chemical refineries adjacent to the respiratory bronchiole, with sparing of at least some alveoli
Paper mills between adjacent bronchioles
Power plants Grade 3: Fibrotic thickening of the walls of all alveoli between ≥2 adjacent respiratory
Railroad operation/maintenance bronchioles
Shipbuilding/ship repair Grade 4: Honeycomb changes
Steel and other molten metal manufacture
US Navy/Merchant Marine *An average score is obtained for an individual case by adding the scores for each slide (0–4) and
then dividing by the number of slides examined.
From Roggli VL, Gibbs AR, Attanoos R, et al. Pathology of asbestosis—an update of the diagnostic
criteria. Report of the Asbestosis Committee of the College of American Pathologists and Pulmonary
Pathology Society. Arch Pathol Lab Med. 2010;134:462–480.

Figure 10.31  Pleural plaque. The gross appearance has been likened to that of candle
wax drippings.

accompanied by asbestos bodies, for which the designation asbestos-

airways disease has been proposed (Box 10.3 and Fig. 10.32).17 As the
Figure 10.30  Asbestosis. The lower lobe parenchyma shows patchy fibrosis. Visceral
fibrotic process progresses in asbestosis, it extends distally beyond the
pleural thickening also is evident (arrowhead). (From Roggli VL, Oury TD, Sporn TA, eds. bronchiolar walls to the alveolar ducts and proximally to the membranous
Pathology of Asbestos-Associated Diseases. 2nd ed. New York: Springer; 2004, with (terminal) bronchioles. The fibrosis also extends radially to involve
permission.) alveolar septa distant from the respiratory bronchiole (Fig. 10.33). In
the most advanced cases of asbestosis, honeycomb fibrosis is present
(Fig. 10.34 and eSlide 10.2), characterized by fibrotic-walled cysts 0.5
by asbestos may be recognized on plain films, high-resolution computed to 1 cm in diameter lined by bronchiolar epithelium and often containing
tomography (HRCT) is considered to be a more sensitive and specific pools of mucus. Alveolar macrophages are sometimes so prominent as
modality for the radiographic evaluation of asbestosis.20 to suggest a diagnosis of desquamative interstitial pneumonia (DIP).
In some cases multinucleated giant cells may be identified within either
Pathologic Findings the interstitium or the alveolar spaces (Fig. 10.35). Rarely hyperplastic
The fibrosis in asbestosis demonstrates a fine reticular pattern, and the alveolar type II pneumocytes may contain cytoplasmic hyaline (Fig.
macroscopic appearance of the lungs ranges from normal to severely 10.36) reminiscent of that found in the cytoplasm of hepatocytes in
scarred and shrunken (Fig. 10.30) with evidence of honeycombing.21,22 alcoholic liver disease.
Asbestosis is usually most severe in the lower lung zones, and accompany- The hallmark of asbestos exposure is the asbestos body, a rodlike,
ing overlying visceral pleural fibrosis is frequently present. Parietal beaded, or dumbbell-shaped structure with a golden-brown coating
pleural plaques, which are frequently bilateral (Fig. 10.31), are present and a thin, translucent core.23 Asbestos bodies are typically found in
in the vast majority of cases and may be calcified. Although diffuse the peribronchiolar interstitium (Fig. 10.37), but with heavy exposure,
pleural fibrosis and plaques serve as a suggestive indicator of an asbestos these may be seen in the alveolar spaces (Fig. 10.38). Detection of
etiology of pulmonary fibrosis, the term asbestosis should not be applied asbestos bodies may be facilitated by the use of iron stains, which impart
to these pleural abnormalities when they occur in the absence of a deep blue color (Fig. 10.39). Asbestos bodies may also be seen in
parenchymal disease. sputum (Fig. 10.40) and thoracic lymph nodes (Fig. 10.41) of patients
Histologically the earliest manifestation of asbestos-associated with heavy exposure to asbestos. Pleural plaques consist of layers of
parenchymal disease is fibrosis of the walls of respiratory bronchioles acellular hyalinized collagen arranged in a “basket-weave” pattern

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A
Figure 10.33  Asbestosis. Peribronchiolar fibrosis extends into adjacent alveolar septa.
Centrilobular emphysema and visceral pleural fibrosis (top) are also seen.

B
Figure 10.32  Asbestosis. (A) The histologic hallmarks of asbestosis are peribronchiolar
fibrosis accompanied by asbestos bodies. (B) Numerous asbestos bodies are present
within a fibrotic alveolar septum in this case with heavy asbestos exposure. Note the
variable beaded, rodlike, and dumbbell shapes.

Figure 10.34  Asbestosis. In a more advanced case, honeycombing (arrowhead) is seen

in addition to lower lobe fibrosis.

Figure 10.35  Asbestosis. A curvilinear asbestos body is seen lying within an interstitial Figure 10.36  Asbestosis. Type II pneumocytes demonstrate cytoplasmic hyaline.
giant cell in this transbronchial biopsy specimen.

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10

Figure 10.37  Asbestosis. In a transbronchial biopsy, interstitial fibrosis and an asbestos

body (upper left) can be seen.

Figure 10.40  Asbestosis. Asbestos bodies in a sputum cytology specimen.

Figure 10.38  Asbestosis. Asbestos bodies are present within an alveolar space in this
case of severe asbestosis.

Figure 10.41  Asbestosis. A section from a thoracic lymph node from a heavily exposed
individual contains numerous asbestos bodies.

Figure 10.39  Asbestosis. In this iron-stained section of lung, an asbestos body has a
characteristic beaded morphology and deep blue color.
Figure 10.42  Pleural plaque. Pleural plaque showing the typical composition of layers
(Fig. 10.42). Visceral pleural fibrosis may show this pattern or appear of acellular hyalinized collagen arranged in a “basket-weave” pattern.
as compact layers of collagen. A mild lymphocytic infiltrate sometimes
accompanies the fibrosis. (Figs. 10.44 and 10.45).24 In cases with diffuse pulmonary fibrosis where
Digestion procedures have been developed for quantifying the content asbestos bodies are not identified in histologic sections, the fiber burden
of asbestos in lung tissue (Fig. 10.43). Any of the commercial forms of is typically more than 2 standard deviations below the mean value.25
asbestos (chrysotile and amphiboles) may be identified in lung tissue Polarizing microscopy is not useful for the detection of asbestos in
from patients with asbestosis by means of analytic electron microscopy histologic sections.

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Figure 10.43  Asbestosis. Asbestos bodies from a lung tissue digest on a Nuclepore Figure 10.44  Asbestosis. Scanning electron microscopy image of an asbestos body.
filter. (From Roggli VL, Oury TD, Sporn TA, eds. Pathology of Asbestos-Associated Diseases. Note the thin, beaded appearance.
2nd ed. New York: Springer; 2004, with permission.)

A B

C
Figure 10.45  Asbestosis. Energy-dispersive x-ray analysis spectra showing characteristic elemental composition of types of
asbestos. (A) Amosite has a prominent peak for silicon (Si) as well as peaks for magnesium (Mg) and iron (Fe). (B) Crocidolite
shows a peak for sodium (Na) in addition to silicon and iron. (C) Tremolite demonstrates peaks for silicon, magnesium, and
calcium (Ca). (D) Chrysotile exhibits prominent peaks for magnesium and silicon. The peak for platinum (Pt) represents the
coating applied to the specimen prior to electron microscopic examination.

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 Pneumoconioses

Differential Diagnosis
Asbestosis must be distinguished not only from usual interstitial
pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), and other
10
forms of diffuse pulmonary fibrosis but also from peribronchiolar fibrosis
associated with cigarette smoking. UIP is characterized by honeycomb
changes, fibroblastic foci, and the absence of asbestos bodies in histologic
sections (Chapter 8). Honeycomb changes are a rarity in asbestosis; in
our experience, fibroblastic foci are also uncommon. Pleural fibrosis is
much more common in individuals with asbestosis than in those with
UIP. The greater temporal uniformity of asbestosis as compared with
UIP is reminiscent of NSIP, but the fibrosis in NSIP exhibits a greater
degree of spatial uniformity and, in cellular examples, more interstitial
inflammation than asbestosis. The early forms of asbestosis (grades 1
to 2) must be distinguished from both mixed dust pneumoconiosis
Figure 10.46  Silicatosis. Grossly, this lung from a kaolinite worker shows scattered
(MDP) and the form of small-airway disease known as respiratory gray areas of fibrosis in addition to centrilobular emphysema.
bronchiolitis, which is seen in cigarette smokers. The latter, which is
characterized by peribronchiolar fibrosis and pigmented smokers’-type
macrophages, tends to involve membranous (terminal) bronchioles and
is often accompanied by mucous plugging and goblet cell metaplasia.
Asbestos bodies are absent in respiratory bronchiolitis. The peribron-
chiolar fibrosis in grades 1 to 2 asbestosis can also mimic burned-out
Langerhans cell histiocytosis, sarcoidosis, or chronic hypersensitivity
pneumonia, but it is distinguished by the presence of asbestos bodies.
Asbestos bodies must be distinguished from nonasbestos ferruginous
bodies (pseudoasbestos bodies) that instead have broad yellow or black
central cores (Fig. 10.27) (also see the Silicatosis section). The use of
transbronchial biopsy in the diagnosis of asbestosis is controversial.19,24
In our experience, patients with evidence of diffuse pulmonary fibrosis
on plain chest films or HRCT who have pulmonary fibrosis and asbestos
bodies on transbronchial biopsy can be reliably diagnosed as having
asbestosis. Conversely, the absence of asbestos bodies on transbronchial
biopsy does not exclude the possibility that asbestosis is the cause of
pulmonary fibrosis. Figure 10.47  Silicatosis. Area of massive fibrosis with deposits of dust-laden
macrophages.
Silicatosis (Silicate Pneumoconiosis)
Silicatosis is caused by the inhalation of silicates. A variety of silicate
minerals may be encountered in the workplace, usually in the setting
of mining and quarry work. Silicates include nonfibrous silicates such
as talc (see later section titled Talcosis), vermiculite, mica, and kaolinite
as well as fibrous silicates such as fuller’s earth.26–29 MDP occurs among
patients exposed to a mixture of silica and nonfibrous silicates. Silicate
pneumoconiosis has also been described in farm workers in areas with
silicate-rich soil.30

Clinical Presentation
Patients with uncomplicated silicate pneumoconiosis are typically
asymptomatic. With extensive fibrosis, they may be short of breath and
demonstrate restrictive changes on pulmonary function testing. In the
rare case with massive fibrosis, hypoxemia and cor pulmonale may
supervene.

Pathologic Findings
Silicatosis is characterized by irregular deposits of collagen, predominantly Figure 10.48  Silicatosis. A section of lung from a patient with heavy exposure to
in a peribronchiolar and perivascular distribution, associated with kaolin dust demonstrates an area of massive fibrosis with paracicatricial emphysema.
numerous birefringent particulates.8,31 The lungs may be macroscopically
normal in mild disease or may be firm and fibrotic (Fig. 10.46). In
patients with significant exposure to silica in addition to silicates, silicotic
nodules and even massive fibrosis may also be present (Fig. 10.47). (Fig. 10.49). Interstitial fibrosis may also be present, characterized by
Paracicatricial emphysema may sometimes be seen adjacent to areas irregularly contoured, stellate lesions with variable collagenization.
of fibrosis (Fig. 10.48). Nonasbestos ferruginous bodies with broad yellow sheet silicate-type
The histologic findings in silicatosis include perivascular and cores (Figs. 10.50 and 10.51) may be observed in some cases.18,31
peribronchiolar deposits of dust-laden macrophages (dust macules) Examination with polarizing microscopy typically demonstrates

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 Practical Pulmonary Pathology

Figure 10.49  Silicatosis. At higher magnification, dust-laden macrophages are

apparent.
Figure 10.52  Silicatosis. Partial polarization of a fibrotic area demonstrates brightly
birefringent silicate particles. (Courtesy Dr. Thomas V. Colby, Mayo Clinic, Scottsdale,
Arizona.)

Figure 10.50  Silicatosis. Pseudoasbestos ferruginous bodies accompany interstitial

fibrosis in this transbronchial biopsy specimen from a patient who had silicatosis with
exposure to feldspar.

Figure 10.53  Mixed dust pneumoconiosis. The peribronchiolar distribution of fibrosis

seen in this case is typical of mixed dust pneumoconiosis.

A special variant of silicatosis is MDP, defined as the occurrence of

dust macules and stellate (Medusa head) lesions producing so-called
mixed dust fibrotic nodules (Figs. 10.53, 10.54, and eSlide 10.3) with
or without accompanying silicotic nodules.33 For a diagnosis of MDP,
the macules and mixed dust fibrotic nodules should outnumber silicotic
nodules. If silicotic nodules predominate, the preferred diagnosis is
silicosis. MDP can occur in individuals who have worked in the coal
mining industry, most typically those involved in the installation of
roof bolts in coal mine shafts. Analytic electron microscopy in MDP
shows aluminum silicates with varying numbers of silica (SiO2)
particles.

Differential Diagnosis
Figure 10.51  Silicatosis. Pseudoasbestos bodies with broad yellow sheet silicate-type Silicatosis must be distinguished from silicosis, UIP, and NSIP. In cases
cores.
with dust macules, mixed dust fibrotic lesions, and silicotic nodules, a
diagnosis of silicosis should be made when silicotic nodules predominate.
numerous brightly birefringent particulates (Fig. 10.52) associated with UIP has well-defined features that are not seen in silicate pneumoconiosis
macrophages or within stellate lesions. Analytic electron microscopy (Chapter 8). It is important to keep in mind that a few scattered bire-
shows numerous particulates, most of which consist of silicon combined fringent particulates may be found in the lungs of individuals in the
with other elements such as magnesium, aluminum, potassium, calcium, general population, including those with UIP and NSIP. Such findings
or iron.32 should not be confused with those in silicate pneumoconiosis, in which

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10

Figure 10.56  Talcosis. In this example, needle-like talc particles are associated with
an exuberant giant cell response.

Figure 10.54  Mixed dust pneumoconiosis. Dust deposits are evident in this stellate
mixed dust fibrotic nodule. (Courtesy Dr. Thomas V. Colby, Mayo Clinic, Scottsdale,
Arizona.)

Figure 10.57  Talcosis. Partially polarized view of talc, exhibiting a characteristic needle-
like morphology.

Figure 10.55  Mixed dust pneumoconiosis. Partially polarized photomicrograph of a Pathologic Findings
mixed dust fibrotic nodule showing particles with variable birefringence. Macroscopically, the lungs in talcosis may be normal or firm in con-
sistency.37 Histologically, patchy peribronchiolar and perivascular fibrosis
is associated with abundant dust deposits (Fig. 10.56). The particles
numerous brightly birefringent silicate particles are present within dust within these deposits are needle-like and have a bluish-gray color.
macules or mixed dust fibrotic lesions (Fig. 10.55). Examination by polarizing microscopy shows numerous brightly
birefringent, needle-like particles within giant cells (Fig. 10.57), granu-
Talcosis (Talc Pneumoconiosis) lomas, or foci of interstitial fibrosis. Multinucleate giant cells are variably
Talcosis, or talc pneumoconiosis, is a type of silicate pneumoconiosis present in talcosis, and in some cases a granulomatous reaction
with unique morphologic and clinical features. Talc is used in many resembling sarcoidosis is seen. Ferruginous bodies with broad yellow
industries. Typical exposures include those related to mining and milling sheet silicate-type cores may also be seen.18 True asbestos bodies may
as well as the rubber and steel industries. Exposures may also occur also be observed in cases where talc is contaminated with substantial
among individuals who use excessive amounts of talcum powder. Talc amounts of asbestos (anthophyllite or tremolite). Similarly, silicotic
is a filler in many medications intended for oral consumption. It may nodules may be seen when there is substantial contamination with
reach the lungs by the vascular route in individuals who intravenously quartz.
inject crushed tablets. Talc is also frequently used for pleurodesis and Intravenous drug abuse talcosis is characterized by the accumulation
may be observed in radical extrapleural pneumonectomy or autopsy of numerous talc granulomas within the pulmonary vasculature and
specimens from patients with malignant mesothelioma. alveolar septal walls (Figs. 10.58 and 10.59). PMF has been reported in
some cases.35 Concomitant paracicatricial emphysema may be pro-
Clinical Presentation nounced.36 Accumulations of talc can also be seen in talc pleurodesis,
Patients are often asymptomatic, but fatal pulmonary fibrosis has been which is characterized by deposits of talc (Figs. 10.60 and 10.61) within
reported among talc miners and millers.34 Intravenous drug abusers the pleura that are associated with macrophages and are also accompanied
may develop pulmonary hypertension, massive fibrosis, or paracicatricial by a giant cell reaction.38
emphysema with spontaneous pneumothorax as a complication of Analytic electron microscopy in talcosis demonstrates platy particles
massive intravascular deposition of talc within the lungs.35,36 composed of magnesium and silicon (Figs. 10.62 and 10.63).39

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 Practical Pulmonary Pathology

Figure 10.58  Intravenous talcosis. Faintly blue-gray talc particles occupy cleftlike spaces. Figure 10.61  Talc pleurodesis. Partial polarization of the case in Fig. 10.60 shows
Note the presence of an asteroid body within a giant cell. numerous platy and needle-shaped birefringent talc particles.

Figure 10.62  Talcosis. In this backscatter electron microscope image, talc has a platy
appearance.
Figure 10.59  Intravenous talcosis. Talc particles appear brightly birefringent under
polarized light.

Figure 10.63  Talcosis. Energy-dispersive x-ray analysis spectrum of a talc particle

demonstrating peaks for silicon (Si) and magnesium (Mg). The peak for platinum (Pt)
represents the coating applied to the specimen before electron microscopic
examination.

within alveolar capillary walls. The talc particles in intravenous talcosis

Figure 10.60  Talc pleurodesis. Talc instilled into the pleural space for therapeutic are on average larger than those observed with inhalational talcosis.
purposes elicited a florid fibrohistiocytic response in this case from a patient with
Often they are too large to be deposited by inhalation. Inhalational
recurrent empyema.
talcosis producing a prominent granulomatous reaction differs from
sarcoidosis in the presence of numerous, long, needle-like birefringent
Differential Diagnosis crystals as compared with the smaller and sparser needle-like particles
Inhalational talcosis must be distinguished from intravenous talcosis of endogenous calcium carbonate that are sometimes seen in sarcoidosis.
and sarcoidosis. In inhalational talcosis, the deposits are primarily peri- In difficult cases, analytic electron microscopy may be required to make
vascular and peribronchiolar, and intraalveolar ferruginous bodies may the distinction. The fibrohistiocytic reaction to talc pleurodesis may
be observed. In intravenous talcosis, talc deposits are intravascular and superficially resemble areas of sarcomatoid mesothelioma. The distinction

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 Pneumoconioses

can be made by the observation of foreign body giant cells and numerous consists predominantly of iron oxide, is typically dark brown to black,
platy birefringent particles in talc pleurodesis. often with a distinctive golden-brown halo (Fig. 10.66). The pigment
may be found in macrophages, in the interstitium, or in both, with very
10
Siderosis little fibrous response. Although there have been rare examples of
Siderosis refers to the accumulation of exogenous iron particulates within nodular fibrosis in the lungs of hematite (iron-containing ore) miners
the lung parenchyma. This disease occurs primarily among hematite that contained little or no silica, the finding of significant amounts of
miners, iron foundry workers, and welders. Miners and foundry workers fibrosis should prompt a search for evidence of exposure to asbestos
may be exposed to significant amounts of silica in the workplace, resulting or silica (Figs. 10.67 and 10.68).42 Ferruginous bodies may be observed
in siderosilicosis, which is characterized by histologic features of both in some cases (Figs. 10.69 and 10.70).18 These may have black iron oxide
siderosis and silicosis. cores, particularly in iron foundry workers (Fig. 10.71), or broad yellow
sheet silicate cores in welders. True asbestos bodies may also be observed
Clinical Presentation if there has been significant exposure to asbestos, as with shipyard
Iron is minimally fibrogenic, so even patients with heavy exposures are welders.
typically asymptomatic. Chest x-rays may suggest interstitial fibrosis Iron oxide pigment is typically nonrefringent when viewed with
owing to shadows cast by the deposits of iron pigment.40 Patients with polarizing microscopy. Analytic electron microscopy demonstrates
significant exposures to silica or asbestos in addition to iron may spherical particles with prominent peaks for iron (Figs. 10.72 and 10.73).
demonstrate clinical features related to the inhalation of such dusts.41
Differential Diagnosis
Pathologic Findings Siderosis must be distinguished from chronic passive congestion of the
Iron pigment imparts a reddish-brown color to the lung parenchyma.42 lungs and from anthracosis (perivascular and peribronchiolar deposits
Because iron is minimally fibrogenic, there is typically no increase in of anthracotic pigment). Chronic passive congestion manifests as
firmness in pure siderosis. However, in cases in which there is con- intraalveolar accumulation of numerous hemosiderin-laden macrophages.
comitant exposure to significant amounts of silica or asbestos, excess Although both hemosiderin and exogenous iron pigment that has been
collagen may be deposited (Fig. 10.64). ferruginized in vivo stain with Prussian blue, hemosiderin lacks the
The histologic hallmark of siderosis is perivascular and peribron- dark brown to black centers characteristic of iron oxide. At low magnifica-
chiolar deposition of iron pigment (Fig. 10.65).43 This pigment, which tion, iron oxide deposits may resemble anthracotic pigment. However,
anthracotic pigment is black throughout, lacking the golden-brown rim
characteristic of iron oxide.

Figure 10.64  Siderosilicosis. This case demonstrates welder’s pigment (iron oxide) as
well as nodular fibrosis typical of siderosilicosis. A

B
Figure 10.66  Siderosis. (A) Detail of iron oxide, or welder’s pigment, which appears
Figure 10.65  Siderosis. Perivascular pigment deposition is seen in this histologic section brown-black with a golden-brown halo. (B) In contrast to welder’s pigment, hemosiderin
taken from the lung of a welder. is typically intraalveolar and lacks black central cores.

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 Practical Pulmonary Pathology

Figure 10.67  Siderosilicosis. A Masson trichrome stain demonstrates the whorled Figure 10.68  Siderosilicosis. The iron pigment appears deep blue in this iron-stained
appearance of this heavily pigmented silicotic nodule. section of the silicotic nodule depicted in Fig. 10.67.

Figure 10.69  Siderosis. Pseudoasbestos bodies with broad yellow sheet silicate cores Figure 10.70  Siderosis. Iron-stained section of lung from the same patient as in Fig.
are seen in this case from a welder. 10.69 demonstrates numerous pseudoasbestos bodies.

Figure 10.71  Siderosis. Pseudoasbestos body on a tissue digestion filter from the lung
of an iron foundry worker. Note the stout, irregularly shaped black iron oxide core.

Figure 10.72  Siderosis. Scanning electron micrograph of iron oxide particles from a
welder’s lung.

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 Pneumoconioses

10

Figure 10.73  Siderosis. Energy-dispersive x-ray analysis spectrum of iron oxide particles
showing predominant peak for iron (Fe).
Figure 10.75  Aluminosis. An accumulation of dust-laden macrophages surrounds a
pulmonary vessel.

Figure 10.74  Aluminosis. Scattered areas of fibrosis are present in the lungs of this
aluminum arc welder.
Figure 10.76  Aluminosis. Detail of dust-laden macrophages, showing the gray-brown
granular appearance typical of aluminum oxide.
Aluminosis
Aluminosis is a pneumoconiosis caused by the inhalation of aluminum-
containing dusts. Although aluminum is relatively ubiquitous within
the environment, aluminosis is a rare disease. Hypersensitivity to
aluminum is believed to play a role in the pathogenesis of aluminosis.
Substantial exposure to aluminum-containing dust may occur in the
setting of aluminum smelting, manufacture of aluminum oxide (corun-
dum) abrasives, aluminum polishing, and aluminum arc welding.44–46

Clinical Presentation
Aluminosis in which interstitial fibrosis is the dominant tissue reaction
may manifest as dyspnea on exertion and restrictive changes on pul-
monary function testing. Fatal cases with severe interstitial fibrosis have
been reported.46

Pathologic Findings
Figure 10.77  Aluminosis. Amorphous eosinophilic material fills the alveoli in a pattern
Macroscopically, the lung parenchyma in aluminosis ranges from
similar to that of pulmonary alveolar proteinosis. Interstitial accumulations of dust-laden
essentially normal to heavy and grayish black with dense fibrotic areas
macrophages are also present.
scattered throughout (Fig. 10.74). A metallic sheen, resembling tarnished
aluminum, has been described in some cases.
Histologic examination discloses perivascular and peribronchiolar observed.50 Rare cases have been described with an alveolar proteinosis-
accumulations of dust-laden macrophages (Fig. 10.75). The dust is like pattern (Figs. 10.77 and 10.78) similar to that seen in acute
refractile and gray to brown (Fig. 10.76). Tissue reaction to aluminum silicoproteinosis.43
ranges in degree from nil to interstitial fibrosis (eSlide 10.4) to granu- Aluminum dust is nonrefringent when examined by polarizing
lomatous inflammation.46–49 Cases with a prominent granulomatous microscopy. Analytic electron microscopy shows electron-dense spherical
response may mimic sarcoidosis. Areas resembling DIP may also be particles (Figs. 10.79 and 10.80) composed of aluminum (Fig. 10.81).

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 Practical Pulmonary Pathology

Figure 10.78  Aluminosis. Higher-magnification view showing the characteristic granular

appearance of aluminum-laden macrophages.

Figure 10.81  Aluminosis. Energy-dispersive x-ray analysis spectrum in a case of aluminosis

demonstrates a peak for aluminum only (AL).

Box 10.4  Uses for Tungsten Carbide

Alloys
Armaments
Ceramics
Circular saw blades
Cutting tools
Drilling equipment

Differential Diagnosis
Dust deposits of aluminum must be distinguished from kaolinite (a form
Figure 10.79  Aluminosis. Transmission electron micrograph showing an alveolar type of aluminum silicate; see earlier section titled Silicatosis) and smoker’s
II cell overlying a dust-filled interstitial macrophage. macrophages. The dust deposits in kaolin worker’s pneumoconiosis are
fine and tan, whereas aluminum is more refractile and gray to brown in
color. In difficult cases, analytic electron microscopy may be required to
make the distinction. Smoker’s macrophages are located predominantly
within the alveolar spaces rather than the interstitium and are typically
associated with scattered black dotlike carbon particles. Aluminum-induced
granulomatosis must be considered in the differential diagnosis of sar-
coidosis. In addition, aluminum exposure must be considered in cases
with a pulmonary alveolar proteinosis pattern. In such cases, the presence
of aluminum dust deposits is a useful differentiating feature.

Hard Metal Lung Disease

Tungsten carbide is used in the manufacture of cutting tools, drilling
equipment, armaments, alloys, and ceramics (Box 10.4). Cobalt is used
as a binder and may constitute up to 25% of the final product by weight.
Hard metal lung disease occurs as a consequence of the inhalation of
hard metal dust, with cobalt being the suspected causative agent of
Figure 10.80  Aluminosis. In this transmission electron micrograph of an aluminum- disease. Exposure may occur during the manufacturing process of hard
containing macrophage, the aluminum particles appear spherical and electron-dense. metal–containing products or during their use.51 Disease has also been
(From Roggli VL. Rare pneumoconioses: metalloconioses. In: Saldana MJ, ed. Pathology reported in diamond polishers who had exposure only to cobalt and
of Pulmonary Disease. Philadelphia: Lippincott; 1994:411–422, with permission.) no exposure to hard metal dust.52,53

Clinical Presentation
Workers with hard metal lung disease present with dyspnea of insidious
onset and restrictive changes, with small lung volumes on pulmonary

354
 Pneumoconioses

10

Figure 10.82  Hard metal pneumoconiosis. At low magnification, the interstitium appears Figure 10.84  Hard metal pneumoconiosis. This bronchoalveolar lavage fluid from a
widened, accompanied by alveolar filling. patient with hard metal pneumoconiosis contains multinucleate giant cells. (From
Tabatowski K, Roggli VL, Fulkerson WJ, et al. Giant cell interstitial pneumonia in a
hard-metal worker: cytologic, histologic and analytical electron microscopic investigation.
Acta Cytol. 1988;32:240–246, with permission.)

Figure 10.83  Hard metal pneumoconiosis. This example demonstrates interstitial

pneumonia with hyperplastic type II pneumocytes and multinucleated giant cells in
alveolar spaces. (Courtesy Dr. Thomas V. Colby, Mayo Clinic, Scottsdale, Arizona.)

Figure 10.85  Hard metal pneumoconiosis. Along with multinucleated giant cells,
function testing. Diffusely increased interstitial markings are observed macrophages fill alveolar spaces in a pattern resembling that of desquamative interstitial
on plain chest films and CT scans. Disease develops in less than 1% of pneumonia. (Courtesy Dr. Thomas V. Colby, Mayo Clinic, Scottsdale, Arizona.)
those exposed, suggesting that hypersensitivity to cobalt is the underlying
pathogenic mechanism. Workers may also present with asthma that
predates interstitial lung disease by months to years. Hard metal lung
disease has been reported to recur after lung transplantation without
additional exposure.54

Pathologic Findings
Macroscopically, the lungs in hard metal lung disease are small and
fibrotic. Microscopically, hard metal lung disease is almost synonymous
with giant cell interstitial pneumonia,55 once considered to be one of
the idiopathic interstitial pneumonias. In this disorder, the alveolar
septa are thickened and fibrotic and lined by hyperplastic type II
pneumocytes (Figs. 10.82 and 10.83). A moderate chronic inflammatory
infiltrate is present. Multinucleated giant cells are a conspicuous feature
(Fig. 10.84) and are found both within the alveolar spaces and lining
the alveolar septa. Alveolar macrophages are present in increased
numbers, and in some cases a pattern reminiscent of DIP is observed
(Fig. 10.85). Occasionally the overall pattern mimics that of UIP, with
areas of microscopic honeycombing (Figs. 10.86 and 10.87). The fibrotic Figure 10.86  Features reminiscent of usual interstitial pneumonia in a case of tungsten
and inflammatory reaction may be accentuated around bronchioles. carbide pneumoconiosis include severe interstitial fibrosis and honeycombing.

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 Practical Pulmonary Pathology

Figure 10.87  Hard metal pneumoconiosis. Detail of the case shown in Fig. 10.86,
demonstrating honeycomb cysts filled with macrophages.
Figure 10.89  Hard metal pneumoconiosis. The metal particles shown in Fig. 10.88
appear as dark dots in this backscatter electron microscopic image. (Courtesy Dr. Frank
Johnson and Dr. Jose Centano, Armed Forces Institute of Pathology, Washington, DC.)

Figure 10.90  Hard metal pneumoconiosis. Energy-dispersive x-ray analysis spectrum

demonstrates a large peak for tungsten, also known as wolfram (W). Ca, Calcium; Fe,
iron. (Reprinted with permission from Sporn TA, Roggli VL: A hard [metal] case: value
Figure 10.88  Hard metal pneumoconiosis. Scanning electron microscopy image of of analytical scanning electron microscopy. Ultrastruct Pathol. 2016;40:147-150.)
alveolar macrophages shows small electron-dense metal particles. (Courtesy Dr. Frank
Johnson and Dr. Jose Centano, Armed Forces Institute of Pathology, Washington, DC.)
cells of hard metal lung disease. DIP can occur in patients with no
identifiable exposure to cobalt.56a
Dust deposits are not readily identified by either routine or polarizing Transbronchial biopsy and bronchoalveolar lavage may be useful in
light microscopy. The individual metal particles can be observed by the diagnosis of hard metal lung disease.57 Analytic electron microscopy
analytic electron microscopy (Figs. 10.88 and 10.89).56 Tungsten particles can be performed on either of these types of specimens and may
are most common, followed by titanium and tantalum (Fig. 10.90). demonstrate the characteristic profile of metallic elements.
Cobalt may or may not be identified because its water solubility makes
it susceptible to removal from tissue during fixation and processing. Berylliosis
Berylliosis is a granulomatous lung disease caused by the inhalation of
Differential Diagnosis beryllium-containing dust.58,59 Beryllium is used in the aerospace industry
Hard metal lung disease must be distinguished from UIP, DIP, and in the manufacture of structural materials, guidance systems, optical
hypersensitivity pneumonitis. The presence of intraalveolar and alveolar devices, rocket motor parts, and heat shields. It is also used in the
septal giant cells, some of which may have a bizarre appearance, and manufacture of ceramic parts, thermal couplings, and crucibles and as
the absence of honeycomb changes favor hard metal disease. In the a controller in nuclear reactors (Box 10.5). Exposure may occur in any
absence of giant cells, analytic electron microscopy may be required to of these industries as well as in the mining or extraction of beryllium
confirm the diagnosis. In contrast with hard metal lung disease, DIP ores.60–62 Historically beryllium was used in the manufacture of fluorescent
has a monotonous pattern with minimal interstitial fibrosis, and although lightbulbs, which accounted for most of the initial reports of
a few giant cells can be seen in DIP, lining of the alveolar septa by berylliosis.63
frequent giant cells is not a feature of DIP. Hypersensitivity pneumonitis
is characterized by an interstitial chronic inflammatory infiltrate associ- Clinical Presentation
ated with small clusters of interstitial giant cells that form ill-defined Patients with berylliosis present with insidiously progressive dyspnea.
granulomas, as opposed to the intraalveolar or alveolar septal giant Pulmonary function testing shows restriction with diminished diffusing

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 Pneumoconioses

Box 10.5  Uses of Beryllium

Aircraft brakes, engines 10

Ceramics
Electrical components
Inertial guidance systems
Laser tubes
Nuclear reactors
Rocket motors
Spark plugs
Turbine rotor blades
Weapons
X-ray tube windows

Figure 10.92  Berylliosis. The granulomas in berylliosis are compact and lack necrosis.
(From Roggli VL, Shelburne JD. Pneumoconioses, mineral and vegetable. In: Dail DH,
Hammar SP, eds. Pulmonary Pathology. 2nd ed. New York: Springer-Verlag; 1994:867–900,
with permission.)

Figure 10.91  Berylliosis. The presence of numerous granulomas is characteristic of

berylliosis. (Courtesy Dr. Fred Askin, Johns Hopkins University, Baltimore, Maryland.)

capacity. Plain films of the chest show a fibronodular process. In lon-

gitudinal studies of exposed individuals, less than 1% to 11% develop
berylliosis.64 Beryllium hypersensitivity with the development of a
beryllium-specific cell-mediated immune response has therefore been
postulated as the likely pathogenic mechanism, as in the diseases caused
by exposure to aluminum and hard metal. In vitro reactivity of peripheral
Figure 10.93  Berylliosis. In addition to granulomatous inflammation, a chronic interstitial
blood or bronchoalveolar lavage lymphocytes to beryllium salts has inflammatory infiltrate is seen. (Courtesy Dr. Thomas V. Colby, Mayo Clinic, Scottsdale,
been used as part of the diagnostic work-up.65 Arizona.)

Pathologic Findings
Macroscopically, the lungs in chronic berylliosis are small and fibrotic
and may show honeycomb changes. Bilateral hilar lymphadenopathy
may be present. Microscopically, there are well-formed nonnecrotizing
granulomas (Figs. 10.91 and 10.92). A chronic interstitial inflammatory
infiltrate typically is present (Fig. 10.93). Granulomas may also be found
in hilar lymph nodes. Schaumann bodies (Fig. 10.94) and asteroid bodies
(Fig. 10.95) within multinucleated giant cells are observed in some
cases.42,43
Beryllium is a lightweight metal that may be detected by analytic
electron microscopy.66 Other techniques—such as wet chemical analysis,
electron energy loss spectrometry, or ion or laser microprobe mass
spectrometry—are also used for detection.2 Polarizing microscopy is
not useful in the diagnosis of berylliosis.

Differential Diagnosis
Berylliosis must be distinguished from sarcoidosis and hypersensitivity Figure 10.94  Berylliosis. A Schaumann body, with its characteristic basophilic laminations,
pneumonitis. Sarcoidosis closely resembles berylliosis histologically; is observed within a giant cell (lower left). (From Roggli VL. Rare pneumoconioses:
therefore a high index of suspicion for exposure to beryllium and a metalloconioses. In: Saldana MJ, ed. Pathology of Pulmonary Disease. Philadelphia:
thorough occupational history are necessary to arrive at the correct Lippincott; 1994:411–422, with permission.)

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 Practical Pulmonary Pathology

Figure 10.95  Berylliosis. This granuloma features a giant cell containing an asteroid Figure 10.96  Rare earth pneumoconiosis. Diffuse interstitial fibrosis with honeycomb
body (upper center). (From Roggli VL. Rare pneumoconioses: metalloconioses. In: Saldana cyst formation in a pattern reminiscent of that seen in usual interstitial pneumonia.
MJ, ed. Pathology of Pulmonary Disease. Philadelphia: Lippincott; 1994:411–422, with
permission.)

diagnosis. Hypersensitivity pneumonitis is associated with a more intense

lymphocytic interstitial and peribronchiolar infiltrate and lacks the
well-formed granulomas observed in berylliosis.

Rare Earth Pneumoconiosis

Rare earth (or cerium oxide) pneumoconiosis is an uncommon disease
caused by the inhalation of rare earth metals, primarily cerium oxide.
Only about 20 cases have been reported, and descriptions of the
pathologic findings are sparse. Most patients with rare earth pneumo-
coniosis have been employed in settings in which they were exposed
to dust from carbon arc lamps. Two patients were exposed to cerium
oxide in an extraction plant, two patients used cerium oxide rouge to
polish lenses, and one patient was a producer of glass rubbing polish.67–70

Clinical Presentation
The clinical presentation ranges from no symptoms to insidiously Figure 10.97  Rare earth pneumoconiosis. Backscatter electron microscopy image of
electron-dense cerium oxide particles.
progressive dyspnea. Chest films show a diffuse interstitial pattern.
Pulmonary function testing shows a restrictive or mixed restrictive/
obstructive pattern and reduced diffusion capacity. The rarity of this
disease suggests hypersensitivity to cerium as the pathogenic discussion, several uncommon and recently recognized pneumoconioses
mechanism. are presented in this section.
Acute high-intensity exposure to cadmium results in acute respiratory
Pathologic Findings distress syndrome, whereas chronic exposure is purported to cause
The spectrum of histopathologic features includes granulomatous disease emphysema.71,72 Most reports on the pulmonary effects of chronic
and interstitial fibrosis.67 The fibrosis is similar to that observed with cadmium exposure appear not to have taken smoking as a confounding
UIP or NSIP (Fig. 10.96). Pigmented dust deposits may be observed factor into consideration.73,74 In addition to being a major cause of
with light microscopy, although these may be sparse. Cerium oxide is emphysema, cigarette smoking is itself a source, albeit small, of cadmium
birefringent on polarizing microscopy. Analytic electron microscopy exposure (≈2 µg per cigarette).75–77 One study that reported an increased
demonstrates rare earth metals, primarily cerium and to a lesser degree rate of emphysema in workers exposed to cadmium did control for
lanthanum, samarium, and neodymium (Figs. 10.97 and 10.98). smoking but unfortunately included only clinicoradiographic data and
no histopathologic descriptions.78
Differential Diagnosis Granulomatous interstitial inflammation and nodular fibrosis
Rare earth pneumoconiosis is most readily confused with UIP or NSIP. reminiscent of silicosis have been reported in some vineyard workers.79,80
Sarcoidosis may be considered if there is a prominent granulomatous Vineyard sprayer’s lung is believed to be caused by chronic exposure
reaction. The diagnosis can be made on the basis of a thorough occu- to copper sulfate, a main constituent of fungicidal solutions commonly
pational history and the detection of rare earth compounds in lung used in viticulture. Histochemical stains for copper reportedly highlight
tissue by analytic electron microscopy. the dust within macrophages and fibrotic nodules.79
Exposure to silicon carbide (carborundum), a synthetic abrasive,
Other Pneumoconioses has been associated with nodular and diffuse interstitial fibrosis resem-
A myriad of other substances have been implicated as causes of pneu- bling silicosis or MDP.81–83 Abundant dust and ferruginous bodies with
moconiosis. Although an exhaustive list is beyond the scope of this black silicon carbide cores have been described.

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 Pneumoconioses

Counts (×103) Counts (×103)

16 8 10
14 Ce 7 Sn

12 6

10 5

8 Ce 4 Sn

6 3 Si

4 2
Ce Al
Sn
PS Ce S
2 Ce Ce Ce 1 Mg Sn Sn

0 0
0 2 4 6 8 10 0 2 4 6 8 10
Range (keV) Range (keV)

Counts (×103) Counts (×103)

16 4

14
P

12 3
Ce
10

8 Ce 2
La
6
S
4 1
Si Ce
Ce Ca
Al Ce
2

0 0
0 2 4 6 8 10 0 2 4 6 8 10
Range (keV) Range (keV)

Figure 10.98  Rare earth pneumoconiosis. Energy-dispersive x-ray analysis spectra demonstrate peaks for rare earth metals,
including cerium (Ce) (upper left panel) and cerium and lanthanum (La) (lower left panel). Background is shown in the lower
right panel and a tin particle (Sn) in the upper right panel. (From McDonald JW, Ghio AJ, Sheehan CE, et al. Rare earth
[cerium oxide] pneumoconiosis: analytical scanning electron microscopy and literature review. Mod Pathol.
1995;8:859–865.)

A variety of pathologic features, which in some cases appear to cleaning agents, and anticorrosives that are sprayed onto the fabrication
resemble those of silicosis or MDP, have been reported as dental techni- surfaces during the machining process.93 Composed of pure petroleum
cian’s pneumoconiosis.82,84–88 The heterogeneity of reported findings is or a mixture of petroleum or synthetic oils and water, MWFs provide
not surprising in view of the plethora of substances that have been used a lipid-rich substrate for the growth of microorganisms. Fungal and
in dental prostheses, including silica, beryllium, chromium, cobalt, and bacterial antigens in contaminated MWFs have been implicated in
molybdenum. outbreaks of hypersensitivity pneumonia in MWF-exposed workers,
Exposure to oil mists or fine sprays in certain machining and engineer- with recent outbreaks attributed to nontuberculous mycobacterial antigens
ing applications, particularly oils low in viscosity or high in mineral oil (Fig. 10.99).94–96
content, has been reported to cause exogenous lipoid pneumonia. The Although inhalational exposure to certain metals—including tin,
histologic features are similar to those of mineral oil aspiration.89–92 barium, and titanium dioxide (rutile)—can produce striking dense
Metalworking fluids (MWFs) are used extensively in automotive nodules on chest imaging, the pneumoconioses they induce are gen-
parts manufacturing and other metalworking industries as coolants, erally considered benign because only macules of birefringent dust

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Figure 10.99  Metalworking fluid hypersensitivity pneumonia. Collections of peribron- Figure 10.101  Flavorings-related lung disease. Bronchiolitis obliterans, characterized
chiolar granulomas are evident. In this example, scattered dust particles are present by mural bronchiolar fibrosis, in a microwave popcorn plant worker. (Courtesy Dr. William
within the granulomas. (Courtesy Dr. Thomas V. Colby, Mayo Clinic, Scottsdale, Arizona.) Travis, Memorial Sloan-Kettering Cancer Center, New York.)

NSIP.102 The typically lymphocyte-rich nature of the pathologic changes

in flock worker’s lung raises considerations of Sjögren-related interstitial
lung disease, lymphocytic interstitial pneumonia, lymphoma, and chronic
hypersensitivity pneumonia, making occupational history essential.
Unlike hypersensitivity pneumonia, granulomatous inflammation
is not a feature of flock worker’s lung. Initially recognized in former
workers at a microwave popcorn plant and thus dubbed popcorn worker’s
lung, a form of lung disease featuring bronchiolitis obliterans and
occasionally peribronchiolar granulomas, it has subsequently been
reported in workers at food flavorings production plants (Fig.
10.101).104–108 The broader term flavorings-related lung disease has been
invoked as a more accurate designation for these types of exposure.
Although it is possible that other flavoring agents to which workers at
these plants are exposed contribute to the development of this condition,
exposure data and animal inhalational studies suggest that diacetyl
(2,3-butanedione), a principal component of butter flavoring, plays a
causal role.109
Indium, in the form of indium–tin oxide, is used in the manufacture
Figure 10.100  Flock worker’s lung. Lymphocytic bronchiolitis and lymphoid hyperplasia,
of liquid crystal displays. It has been associated with pulmonary alveolar
sometimes with germinal center formation, as seen in this case, are among the more
proteinosis and proliferative peribronchial fibrosis with cholesterol
frequently reported findings in this condition. (Courtesy Dr. Armando Fraire, University
of Massachusetts, Worcester, Massachusetts.) clefts.110–112
Analysis of the lungs of individuals exposed to dust from the 2001
World Trade Center terrorist attack who have developed interstitial
fibrosis and/or small airways abnormalities has disclosed a variety of
particles with little to no fibrosis are usually seen pathologically.42,97,98 particles such as silicates and asbestos.113,114 A case of acute eosinophilic
One case of pulmonary alveolar proteinosis in a painter who was pneumonia has also been described in association with acute exposure
shown to have a high concentration of titanium in the lungs has been to high levels of World Trade Center dust.115
reported.99 An increased incidence of respiratory symptoms has been reported
Flock worker’s lung derives its name from an interstitial lung disease in soldiers who served in the Middle East. Some of these individuals,
that has been reported in some individuals employed in the flocking including a number who were exposed to smoke from sulfur mine fires
industry. Flocking involves the application of short synthetic fibers, in Iraq, had features of constrictive bronchiolitis and peribronchiolar
frequently nylon, onto an adhesive backing, resulting in a plush material. pigment deposition on lung biopsy.116
Respired shards generated in the process of cutting fibers to length with Pulmonary disease caused by polluted indoor air is a vastly under-
a rotary cutter are believed to cause a restrictive process characterized recognized problem.117–125 Cooking indoors with coal or biomass fuels
histologically by lymphoid hyperplasia, lymphocytic bronchiolitis, and such as wood, peat, crop residues, or dung in open-pit fires or poorly
peribronchiolar interstitial inflammation (Fig. 10.100).100–103 A spectrum ventilated stoves is commonplace in developing countries. This practice
of other histologic features and patterns has been reported, including releases numerous particulates, including silicates, into the air. Not
diffuse lymphocytic interstitial inflammation, interstitial fibrosis, surprisingly, most reported cases of this pneumoconiosis, which has
fibroblastic foci, bronchiolitis obliterans organizing pneumonia, and been referred to as hut lung or domestically-acquired particulate lung

360
 Pneumoconioses

10

Figure 10.102  Domestically-acquired particulate lung disease. Extensive interstitial Figure 10.104  Bronchial anthracofibrosis/domestically-acquired particulate lung disease.
fibrosis with abundant entrapped dust particles is seen. This biopsy is from a woman Anthracotic submucosal and peribronchial dust deposition accompanied by densely,
who had recently immigrated to the United States from a developing country, where collagenized mixed dust–type fibrosis of variable density.
for many years she cooked with a poorly ventilated indoor stove that used biomass
fuels. (Courtesy Dr. Thomas V. Colby, Mayo Clinic, Scottsdale, Arizona.)
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106. Kreiss K, Gomaa A, Kullman G, et al. Clinical bronchiolitis obliterans in workers at a microwave- obstructive pulmonary disease due to biomass smoke and tobacco. Am J Respir Crit Care Med.
popcorn plant. N Engl J Med. 2002;347(5):330-338. 2006;173(4):393-397.
107. Akpinar-Elci M, Travis WD, Lynch DA, Kreiss K. Bronchiolitis obliterans syndrome in popcorn 125. Diaz JV, Koff J, Gotway MB, Nishimura S, Balmes JR. Case report: a case of wood-smoke-related
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Multiple Choice Questions 6. Fibrotic nodules in coal worker’s pneumoconiosis differ from those
1. Which ONE of the following statements regarding silicosis is FALSE?
of silicosis by showing:
A. A potential for cavitation
10
A. It can be seen in farmers in the extreme eastern portions of the
B. A complete absence of silica particles
United States.
C. An exclusively subpleural localization
B. The disease predominates in the upper lung fields.
D. A “Medusa head”–like microscopic configuration
C. It is caused by inhalation of crystalline silica.
E. A tendency to regress after inhalation of coal dust ceases
D. It spares the pleura.
E. Pathologic findings include both nodular and diffuse interstitial ANSWER: D
fibrosis.
7. Intrapulmonary ferruginous bodies with a dematiaceous core may
ANSWER: D
be seen in:
A. Asbestosis
2. Secondary alveolar abnormalities in silicosis show a histologic
B. Silicosis
similarity to:
C. Coal worker’s pneumoconiosis
A. Alveolar proteinosis
D. Silicatosis
B. Alveolar microlithiasis
E. All of the above
C. Alveolar sarcoidosis
D. Alpha-1-antitrypsin deficiency ANSWER: C
E. None of the above
8. Which ONE of the following statements regarding asbestosis is
ANSWER: A
FALSE?
A. Pleural plaques alone, in an exposed individual, are diagnostically
3. Which ONE of the following statements regarding silicosis is TRUE?
sufficient.
A. Scanning electron microscopy shows angulated particles in the
B. “Bystander” (household) exposures can rarely cause the disease.
lesions.
C. Pulmonary function testing usually shows a “restrictive”
B. Caseation necrosis is a common finding in silicotic nodules.
pulmonopathy.
C. The presence of numerous Langhans cells supports this
D. High-resolution computed tomography may be necessary for
diagnosis.
diagnosis.
D. Brightly birefringent particles are numerous in polarization
E. Cor pulmonale can be seen clinically in advanced stages of the
microscopy.
disease.
E. Associated alveolar exudates are nonreactive with the periodic
acid–Schiff stain. ANSWER: A
ANSWER: A
9. Which of the following pathologic findings is commonly seen
concomitantly in patients with parenchymal asbestosis?
4. Which ONE of the following statements regarding coal worker’s
A. Bilateral fibrohyaline pleural plaques
pneumoconiosis (CWP; “black lung” disease) is FALSE?
B. Peripherolobular calcification of alveolar walls
A. Its development depends partly on idiosyncratic host factors.
C. Alveolar-proteinosis–like alveolar exudates
B. It may feature the development of small intrapulmonary nodules.
D. Nodular lymphocytic bronchiolitis
C. Particular job types in mines do not correlate with the risk of
E. All of the above
CWP.
D. Patients with CWP may be asymptomatic. ANSWER: A
E. The pleural surface shows foci of accentuated pigmentation.
10. Histopathologic findings in asbestosis may include:
ANSWER: C
A. Peribronchiolar fibrosis
B. Numerous intraalveolar histiocytes
5. Which ONE of the following statements regarding coal worker’s
C. Type II pneumocytic hyperplasia
pneumoconiosis (CWP) is TRUE?
D. Visceral pleural fibrosis
A. The disease predominates in the lower lobes of both lungs.
E. All of the above
B. Nodular lesions in CWP are slate-gray on gross inspection.
C. Lesions of progressive massive fibrosis (PMF) are rock-hard. ANSWER: E
D. Individual lesions of PMF measure no more than 1.5 cm in
diameter. 11. Which of the following is least likely to manifest as a granulomatous
E. Cavitation in nodular CWP lesions may suggest secondary reaction?
tuberculosis. A. Sarcoidosis
B. Aluminosis
ANSWER: E
C. Silicosis
D. Talcosis
E. Berylliosis
ANSWER: C

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12. Pseudoasbestos ferruginous bodies may form on which of the 18. All of the following statements about rare earth pneumoconiosis
following? are correct EXCEPT:
A. Talc A. It is also known as cerium oxide pneumoconiosis.
B. Iron oxides B. The believed causative agent is birefringent on polarizing
C. Feldspar microscopy.
D. Coal particles C. The histopathologic features are similar to desquamative
E. All of the above interstitial pneumonitis.
D. Granulomas may be present.
ANSWER: E
E. All of the above
13. Exposure to aluminum dust may result in all of the following ANSWER: C
EXCEPT:
A. Parietal pleural plaques 19. True or false: Flock worker’s lung is characterized by sarcoid-like
B. Peribronchiolar accumulation of dust laden macrophages granulomas.
C. Interstitial pulmonary fibrosis A. True
D. Granuloma formation B. False
E. Alveolar-proteinosis–like reaction
ANSWER: B
ANSWER: A
20. True or false: Hut lung has been reported to occur predominantly
14. True or false: Talc in histologic sections may derive from inhalation in males.
of talc dust, intravenous drug abuse, or talc pleurodesis. A. True
A. True B. False
B. False
ANSWER: B
ANSWER: A

15. Which of the following statements is TRUE? Case 1

A. It is not possible to distinguish welder’s pigment from hemo- eSlide 10.1
siderin in histologic sections.
Sharply circumscribed silicotic nodule characterized by densely hyalinized
B. Iron oxides from arc welding typically result in an exuberant
collagen and dust-containing macrophages at the periphery.
fibrous reaction in the lungs.
a. History: Granite quarry worker with nodule detected on imaging.
C. Exposure to iron oxide particles may occur from mining hematite
b. Pathologic Findings: Sharply circumscribed nodule of hyalinized
or working in a foundry.
collagen with dust-containing macrophages at the periphery.
D. Iron oxides are brightly birefringent when viewed with polarizing
c. Diagnosis: Silicosis.
microscopy.
d. Discussion: Silicotic nodules are the histologic hallmark of silicosis,
E. None of the above
a disease caused by the inhalation of crystalline silica.
ANSWER: C

16. Which of the following statements concerning hard metal lung Case 2
disease is/are TRUE? eSlide 10.2
A. Disease develops in greater than 90% of individuals exposed to Extensive peribronchiolar fibrosis with subpleural honeycombing
hard metals. accompanied by numerous asbestos bodies.
B. It is thought to be due to hypersensitivity to cobalt. a. History: Retired insulator with severe progressive dyspnea and
C. It is characterized by abundant dust deposits on routine reticulonodular infiltrates in the lower lung zones on radiography.
microscopy. b. Pathologic Findings: Severe peribronchiolar interstitial fibrosis with
D. It features interstitial giant cells. focal honeycombing accompanied by beaded and rodlike asbestos
E. All of the above bodies.
c. Diagnosis: Grades 3 to 4 asbestosis.
ANSWER: B
d. Discussion: Asbestosis is caused by the inhalation of asbestos fibers,
resulting in pulmonary interstitial fibrosis.
17. Which of the following statements about berylliosis is FALSE?
A. Well-formed non-necrotizing granulomas are present.
B. Polarizing microscopy is not useful for the diagnosis. Case 3
C. It develops in less than 5% of individuals exposed to eSlide 10.3
beryllium.
Stellate mixed dust fibrotic lesions featuring abundant dust-laden
D. Chronic interstitial inflammatory is typically absent.
macrophages.
E. It resembles sarcoidosis histologically.
a. History: Former coal miner with irregular opacities on imaging.
ANSWER: D b. Pathologic Findings: Stellate fibrotic lesions with dust-laden
macrophages.
c. Diagnosis: Mixed dust pneumoconiosis.
d. Discussion: Mixed dust pneumoconiosis is a variant of silicatosis
defined by the presence of dust macules and stellate mixed dust
fibrotic nodules.
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Case 4 Case 5
eSlide 10.4 eSlide 10.5 10
Copious macrophages filled with gray-brown granular particulates are Massive peribronchial fibrosis and heavily pigmented mixed dust and
associated with diffuse interstitial fibrosis in an individual with a history silicotic nodules characterize domestically-acquired particulate lung
of aluminum arc welding. disease.
a. History: Male with a history of aluminum arc welding presented a. History: 65-year-old Chinese female never-smoker who had immi-
with progressive dyspnea. grated to the United States 20 years prior presented with life-
b. Pathologic Findings: Diffuse interstitial fibrosis accompanied by threatening hemoptysis.
abundant macrophages with granular gray-brown particulate b. Pathologic Findings: Extensive peribronchial fibrosis with numerous
material. mixed dust and silicotic nodules with resultant bronchial stenosis.
c. Diagnosis: Pulmonary interstitial fibrosis associated with aluminum c. Diagnosis: Domestically-acquired particulate lung disease (hut lung).
arc welding. d. Discussion: Domestically-acquired particulate lung disease is an
d. Discussion: Aluminosis can produce a variety of tissue reactions in underrecognized pneumoconiosis associated with exposure to
the lung, sometimes including interstitial fibrosis. cooking/heating with biomass fuels in poorly ventilated spaces.

364.e3