Twenty Two Flashcards Preview

Respiratory > Twenty Two > Flashcards

Flashcards in Twenty Two Deck (28):

What are restrictive lung diseases and what are some common themes among them?

Restrictive lung diseases are characterized by reduced lung
compliance that requires greater pressure to infl ate the lungs
and, clinically, typically are manifest as dyspnea.

Many such
diseases show thickening of alveolar septa and alveolar epithelial
and endothelial injury that lead to
Q mismatch. With
progression of many such diseases, patients develop severe
hypoxemia and respiratory failure. These are often complicated
with pulmonary hypertension and cor pulmonale
(right ventricular dilatation due to lung disease).


How is ARDS characterized? What about ALI? What is the morphological counterpart of these diseases?

The acute respiratory distress syndrome (ARDS) is a clinical
syndrome characterized by the acute onset of respiratory
distress with hypoxemia, reduced lung compliance, and diffuse
pulmonary infi ltrates in the absence of primary left heart
failure; a less severe form of the syndrome is acute lung
injury (ALI) (Chap. 28). Diffuse alveolar damage (DAD)
is the morphologic counterpart of ALI/ARDS.


What is the pathogenesis of DAD?

The pathogenesis of DAD begins with endothelial damage
or, less frequently, epithelial damage. Within 30 minutes, macrophages
secrete canonical proinfl ammatory cytokines including
TNF-α, IL-1, and IL-8, leading to neutrophil chemotaxis and
activation (Chap. 10). Activated neutrophils secrete oxidants,
proteases, platelet activating factor (PAF), and leukotrienes,
the results of which are tissue damage, edema, inactivation of
pulmonary surfactant, and the formation of hyaline membranes, the morphologic hallmark of DAD (see below). Later, macrophage
secretion of transforming growth factor-beta (TGF-β)
and platelet-derived growth factor (PDGF) causes proliferation
of fi broblasts with subsequent synthesis of collagen. The pathogenesis
of DAD is further discussed in Chap. 28.


What is DAD in the lungs like grossly? Describe the 3 phases of DAD microscopically? What do hyaline membranes consist of?

Morphologically, lungs with DAD show reduced crepitus
and resemble liver in consistency. Early in the course, the
lungs are dense and dark red; as collagen deposition occurs,
their color changes to gray (Fig. 23.1). Microscopically, DAD
shows a spectrum of changes that can be organized into three
phases (Fig. 23.2). The earliest of these is the exudative phase,
with vascular congestion, interstitial and intra-alveolar edema,
alveolar epithelial necrosis, neutrophil margination, dilatation
and/or collapse of alveolar ducts, fi brin thrombi, and hyaline
membranes. Hyaline membranes, the hallmark of DAD, are
composed of edema fl uid and necrotic epithelial cells. Subsequent
to this exudative period is the proliferative phase,
in which there is type 2 pneumocyte hyperplasia as well as
fi broblast infi ltration of the interstitium and the intra-alveolar
exudate (ie, the hyaline membranes). Finally, as fi broblasts
synthesize collagen, DAD enters the fi brotic phase, with
fi brosis of the exudate (also described as organization) and
expansion of the interstitium by fi brosis.


What is the clinical progression of ARDS like? When and how can it be seen clinically?

Clinically, ARDS begins with dyspnea and tachypnea;
early in its course, a chest radiograph may be normal. Subsequently,
the patient develops cyanosis, hypoxemia, and respiratory
failure, at which point a chest radiograph typically shows
diffuse bilateral infi ltrates. As hypoxemia becomes unresponsive
to oxygen therapy, respiratory acidosis often develops. Of
note, oxygen therapy can worsen the alveolar epithelial damage.
ARDS can be complicated by secondary infection of the
hyaline membranes and/or by death, the latter occurring inapproximately 40% of cases in the United States.


What is acute interstitial pneumonia? What is another name for it? What is it like morphologically? What is its mortality rate?

Acute interstitial pneumonia is a rapidly progressive
acute restrictive lung disease with a presentation similar to ARDS
but without a known underlying etiology; an alternate name is
idiopathic ALI-DAD. Morphologically, it closely resembles DAD
and may be indistinguishable from DAD. Mortality rates in various studies have ranged from 33% to 74%. Survivors often
experience complete or near complete recovery.


What is another name for chronic restrictive lung diseases? Why? What do they share in common clinically? Pathogenetically? Morphologically? End stage?

The chronic restrictive lung diseases are also called diffuse
interstitial lung diseases, because changes in the interstitium
dominate the morphologic appearance, and diffuse infi ltrative
diseases, because chest radiographs show diffuse infi ltrates.

Chronic restrictive lung diseases are a heterogeneous group
of disorders without uniform classifi cation, without uniform
terminology, and often without known etiology or pathogenesis.
Nevertheless, they share many clinical and morphological
features and, at end-stage, they may be indistinguishable from
each other. Clinically, patients with chronic restrictive lung
diseases have dyspnea, tachypnea, end-inspiratory crackles,
and eventual cyanosis (Chap. 24). Later, these patients often
develop secondary pulmonary hypertension (Chap. 26) and
right heart failure with cor pulmonale. Pathogenetically, many
of the chronic restrictive lung diseases begin with alveolitis,
leading to distortion of alveolar structure and release of mediators
that incite cell injury and induce fi brosis. Morphologically,
many of the chronic restrictive lung diseases, particularly in
later stages, are characterized by interstitial fi brosis. The endstage
of many of the chronic restrictive lung diseases is the
classic honeycomb lung.


What is idiopathic pulmonary fibrosis and how is it characterized? Pathogenesis? What is it like grossly? Microscopically? Clinically? Treatment?

Idiopathic pulmonary fi brosis (IPF) is a poorly understood,
idiopathic, nongranulomatous chronic restrictive lung
disease that morphologically is characterized by diffuse
interstitial fi brosis. Although many alternate names for the
disease exist, cryptogenic fi brosing alveolitis is the one
most frequently encountered. The pathogenesis of IPF is
poorly understood but appears to involve repeated cycles of
alveolitis (due to an unidentifi ed agent) that are followed by
wound healing with fi broblast proliferation. Grossly, lungs
with well-developed IPF have a pleural surface with a cobblestone
appearance due to wound contraction in interlobular
septa. The cut surface of IPF lungs shows rubbery-to-fi rm,
white patches in subpleural regions and in the interlobular
septa (Fig. 23.3).

Histologically, the morphology of IPF is described as
usual interstitial pneumonia (UIP) (Fig. 23.4). Although
required for a diagnosis of IPF, UIP is not specifi c and can be
seen in other diseases (eg, collagen vascular diseases, asbestosis;
see below). UIP is characterized by regional and temporal
heterogeneity where different lung foci show different
stages of disease. In addition to interstitial fi brosis, magnifi ed
in subpleural zones and interlobular septa, UIP includes characteristic fi broblastic foci and typically shows prominent
type 2 pneumocyte hyperplasia. End-stage UIP shows dilatated
airspaces lined by cuboidal or low columnar epithelium separated
by infl amed fi brous tissue. Patients with IPF typically
present in the fi fth to eighth decade with increasing dyspnea
on exertion and dry cough, followed by hypoxemia, cyanosis,
and digital clubbing. Progression of IPF is unpredictable, but
the mean survival time is approximately three years. The only
defi nitive therapy for IPF is lung transplantation.


What is non specific interstitial pneumonia? What is it like histologically?

Nonspecifi c interstitial pneumonia (NSIP) is an idiopathic,
nongranulomatous lung disease without the defi ning
diagnostic features of better-characterized diseases. Histologically,
NSIP can show a cellular pattern with mild to moderate
expansion of the interstitium by lymphocytes and plasma cells
with either a uniform or patchy distribution [Fig. 23.6(a)].
Alternatively, a fi brosing pattern with diffuse or patchy interstitial
fi brosis is noted [Fig. 23.6(b)]. In contrast to UIP, the
fi brosing pattern of NSIP does typically not show fi broblastic
foci or the regional/temporal heterogeneity of disease.


What is sarcoidosis and how is it characterized? How is the diagnosis made? What is its pathology? What is its epidemiology? What is its etiology? What is its pathogenesis? Genetics? Morphology?

Sarcoidosis is an idiopathic multisystem disease characterized
by granulomatous infl ammation (typically noncaseating)
in many tissues and organs. Since there are many causes
of granulomatous infl ammation—including foreign body, mycobacterial infection, and fungal infection—sarcoidosis is
a diagnosis of exclusion. Though its presentation can include
involvement of virtually any organ, patients typically have
bilateral hilar lymphadenopathy and/or lung involvement.
Sarcoidosis shows a racial bias (black:white of about 10:1)
and a female gender bias. Though the etiology of sarcoidosis
is unknown, its pathogenesis likely involves a type IV hypersensitivity
reaction (cell-mediated, delayed) to a currently
unknown antigen. Familial and racial clustering and association
with certain HLA subtypes imply that development of sarcoidosis may require a genetic predisposition. Many features
of sarcoidosis suggest that it is an infectious disease,
but there is no unequivocal evidence that sarcoidosis has
an infectious etiology. The morphology of sarcoidosis is
nonspecific: noncaseating granulomatous inflammation
(Fig. 23.7).


What is a granuloma? What are the granulomata like in sarcoidosis?

A granuloma is a circumscribed collection of
epithelioid histiocytes [Fig. 23.7(c)]; the term “epithelioid”
is used to describe cells that have more cytoplasm than typical
histiocytes, imparting a resemblance to squamous epithelial
cells. Epithelioid histiocytes can merge with each other, producing a multinucleated giant cell. While multinucleated giant cells
are common in granulomata, not all granulomata contain
them. In sarcoidosis, the granulomata often contain Schaumann
bodies [laminated concretions of calcium and protein,
Fig. 23.7(d)] and asteroid bodies [stellate inclusions within
giant cells, Fig. 23.7(e)]. However, neither Schaumann bodies
nor asteroid bodies are specifi c for sarcoidosis.


What organs do the granulomata of sarcoidosis often involve? What is it like clinically? How does it normally present? What is the prognosis?

As mentioned above, the granulomata in sarcoidosis can
involve virtually any organ but typically involve the pulmonary
interstitium and hilar lymph nodes. Pulmonary involvement is
often complicated by interstitial fi brosis. Other organs that are
commonly involved include skin, eyes, lacrimal glands, salivary
glands, spleen, liver, and skeletal muscle. Clinically, sarcoidosis
is often asymptomatic. If symptomatic, sarcoidosis
ranges from progressive chronicity to periods of activity separated
by periods of remission. Presentation is typically due to respiratory involvement, with dyspnea, cough, chest pain, and
hemoptysis; alternatively, constitutional signs and symptoms
(fever, fatigue, weight loss, anorexia, night sweats) may dominate
the clinical scenario. Specifi c symptoms at presentation
are markedly variable due to the complex of sites showing
involvement. Approximately 65%-70% of patients recover
spontaneously or with steroid therapy and have minimal or
no residual disease, ~20% of patients develop permanent lung
dysfunction or visual impairment, and 10%-15% develop progressive
pulmonary fi brosis with subsequent cor pulmonale or
central nervous system damage.


What is hypersensitivity pneumonitis? How does it begin? What is the acute phase like both clinically and histologically? What is the chronic phase like clinically and histologically? What kind of hypersensitivity reactions are involved in the acute and chronic?

Hypersensitivity pneumonitis is typically an occupational
disease that begins with alveolar damage from exposure
to an organic antigen. The acute phase of the disease occurs
4-6 hours after antigen exposure in a previously sensitized host,
likely represents a type III hypersensitivity reaction (immune complex), and is typifi ed by diffuse and nodular infi ltrates on
chest radiograph, restrictive pattern of pulmonary function
tests, and neutrophilic infl ammation. With continuous antigen
exposure, the disease enters its chronic phase with respiratory
failure, dyspnea, cyanosis, decreased lung compliance, and
decreased total lung capacity. The chronic phase is a type IV
hypersensitivity reaction (delayed, cell-mediated) characterized
histologically by lymphocytes, plasma cells, and foamy
histiocytes in alveoli, alveolar walls, and around terminal
bronchioles; interstitial fi brosis; obliterative bronchiolitis;
and, in about two-thirds of cases, granulomata. Of note, the
eosinophilia that is typical of type I hypersensitivity reactions
is not a signifi cant feature of hypersensitivity pneumonitis. If
the offending antigen is removed during the acute phase, the
disease resolves in weeks. Once the disease has progressed to
its chronic phase, resolution can be slow, and approximately
5% of patients develop respiratory failure and die. Table 23.2
summarizes the myriad diseases that represent forms of hypersensitivity


What is pulmonary eosinophilia? What is the clinical scenario? What is it like morphologically? How are acute eosinohilic pneumonia, simply pulmonary eosinophilia, tropical eosinophilia, secondary chronic pulmonary eosinophilia, and idiopathic chronic eosinophilic pneumonia characterized by?

Pulmonary eosinophilia is a collection of diseases with
similar morphologies of eosinophilic infi ltration of the pulmonary
interstitium and/or alveolar spaces (Fig. 23.9) and similar
clinical scenarios of corticosteroid-responsive fever, night sweats,
and dyspnea. Acute eosinophilic pneumonia with respiratory
failure is an idiopathic illness with rapid onset of fever, dyspnea,
and potentially fatal hypoxemic respiratory failure. Simple pulmonary
eosinophilia (Löffl er syndrome) is characterized by
transient pulmonary eosinophilic infi ltrates and peripheral blood
eosinophilia. Tropical eosinophilia represents a microfi larial
infection. Secondary chronic pulmonary eosinophilia occurs
in a number of settings, including certain infections (parasitic,
fungal, bacterial), drug allergies, asthma, allergic bronchopulmonary
aspergillosis (Chap. 20), and polyarteritis nodosa. Idiopathic
chronic eosinophilic pneumonia is characterized by
interstitial and intra-alveolar lymphocytic and eosinophilic infi ltrates
in peripheral lung fi elds. From the morphologic perspective,
many of these diseases are indistinguishable, thus giving
rise to the morphologic term pulmonary eosinophilia.


What are some smoking related chronic restrictive lung diseases? Describe them morphologically and clinically.

Though smoking-related lung disease is frequently
obstructive (see Chap. 20 for discussions of emphysema and
chronic bronchitis), there are several smoking-related restrictive
lung diseases. Desquamative interstitial pneumonitis
(DIP) and respiratory bronchiolitis-associated interstitial
lung disease are thought of as opposite ends of a spectrum
of interstitial lung disease that may develop in smokers; the
pathogenesis of both is unknown. In DIP [Fig 23.10(a), (b)],
there is mononuclear interstitial infl ammation, an abundance
of airspace macrophages with dusty brown cytoplasmic
pigment, and type 2 pneumocyte hyperplasia. The airspace macrophages in DIP typically clump together, resulting in an
appearance that was historically (and erroneously) interpreted
as desquamated alveolar epithelium. In respiratory bronchiolitis-
associated interstitial lung disease, there is patchy
bronchiolocentric distribution of pigmented macrophages
[Fig. 23.10(c)], and there can be histologic overlap with DIP.
Both DIP and respiratory bronchiolitis-associated interstitial
lung disease present in the fourth to fi fth decade, show a male
gender bias (male:female ratio of about 2:1), may occur with
insidious onset of dyspnea and cough, and improve with cessation
of smoking and steroid therapy.


Describe pulmonary amyloidosis.

Pulmonary amyloidosis can show diffuse deposition of
amyloid in alveolar septa, a pattern typically associated with disseminated
primary amyloidosis or multiple myeloma, or there
may be nodular deposition of amyloid. Pulmonary symptoms
are usually not severe. Morphologically, amyloid is hyaline and
stains with Congo red stain [Fig. 23.11(a), (b)]. Amyloid shows
apple-green birefringence when stained with Congo red and
viewed through a polarized light source [Fig. 23.11(c)].


What is cryptogenic organizing pneumonia? How is it characterized? What is its pathology? What are some etiologies? Treatment?

Cryptogenic organizing pneumonia (COP) is a nonspecifi
c pattern of lung injury characterized by polypoid plugs
of loose fi brous tissue. In contrast to the majority of diseases
discussed in this chapter, in COP the fi brous tissue is not in the
interstitium but rather within lumina of alveolar ducts, alveoli,
and often bronchioles (Fig. 23.12). The distribution of lesions
is typically peripheral (distal). There are many etiologies
of COP including infection (viral, bacterial), collagen
vascular diseases, drug toxicity, toxic inhalants, and bronchial
obstruction. Most patients show gradual improvement with
steroid therapy.


What is PAP? How does it look on radiograph? What are some etiologies for the acquired version? The congenital version? The secondary version? What are the lungs like grossly? Microscopically? Clinically? What is the therapy for adult PAP? Congenital? Prognosis?

Pulmonary alveolar proteinosis (PAP) is a rare disease
with bilateral, patchy, and asymmetric lung involvement manifesting
as opacifi cation on chest radiograph. PAP can be acquired
(being most common with ~90% of cases), congenital, or secondary.
Acquired PAP appears to result from an autoantibody
that inhibits the activity of GM-CSF, thereby impairing macrophage
clearance of pulmonary surfactant. Congenital PAP is
genetically heterogeneous, with the genetic lesion unknown in
most cases; alternatively, congenital PAP can arise in the setting
of mutations in the genes for ATP-binding cassette protein
member A3 (ABCA3), surfactant protein B, GM-CSF, or the
GM-CSF receptor β chain. Secondary PAP can arise in the setting
of hematopoietic disease, malignancy, immunodefi ciency, lysinuric protein intolerance, or acute silicosis (and other pneumoconioses,
see below). Morphologically, whether acquired,
congenital, or secondary, PAP is characterized by enlarged and
abnormally heavy lungs which exude turbid fl uid on sectioning.
Microscopically (Fig. 23.13), there is intra-alveolar accumulation
of dense, granular, eosinophilic material containing lipid
and PAS-positive material. Clinically, PAP presents with insidious
respiratory diffi culty and a cough productive of abundant
gelatinous chunks. With disease progression, dyspnea, cyanosis,
and respiratory insuffi ciency can develop. Therapy for adult PAP
involves lung lavage, and approximately one-half of adults
benefi t from recombinant GM-CSF therapy. Congenital PAP is
fatal in 3-6 months without lung transplantation.


What is the pulmonary involvement in progressive systemic sclerosis, systemic lupus erythematous, and rheumatoid arthrosis? What is the presence of rheumatoid nodules in the setting of pneumoconiosis known as?

Collagen vascular diseases can be complicated by pulmonary
involvement. In progressive systemic sclerosis (scleroderma),
pulmonary injury is typifi ed by diffuse interstitial
fi brosis. In systemic lupus erythematosus (SLE), pulmonary
histopathology typically consists of patchy, transient
parenchymal infi ltrates. In rheumatoid arthritis, pulmonary
involvement can manifest as chronic pleuritis (with or without
a pleural effusion), diffuse interstitial pneumonitis and fi brosis, pulmonary hypertension (Chap. 26), or intrapulmonary
rheumatoid nodules. The presence of rheumatoid nodules
in the setting of pneumoconiosis (see below) is known as
Caplan syndrome.


What is pneumoconiosis? What does its development depend on? What happens to particles

The term pneumoconiosis is broad and refers to non-neoplastic
lung reactions to the inhalation of irritants to the lung. Nonetheless,
many use this term to refer to such lung reactions to
the inhalation of nonorganic mineral dusts. The development
of pneumoconiosis depends on the amount of dust retained in
the lung, particle solubility and physical/chemical reactivity,
and the possible additive effects of other irritants such as cigarette
smoke. The amount of dust retained in the lung following
inhalation has much to do with particle size (Chap. 10).


What is CWP? What is anthracosis? What is it like clinically? Morphologically? What is simple CWP? What is it like clinically? Morphologically? What is complicated CWP? What is it like clinically? Morphologically? What can complicate it and in what ways?

Coal worker’s pneumoconiosis (CWP) can develop
with inhalation of carbon dust. Low-level exposure to coal
dust leads to anthracosis, an asymptomatic accumulation of
carbon pigment with no signifi cant cellular response. With
moderate coal dust exposure, simple CWP can develop that
shows little or no pulmonary dysfunction. With heavy exposure,
however, simple CWP can progress to complicated CWP
with respiratory insuffi ciency. Morphologically, anthracosis
is characterized by accumulation of black pigment in alveolar
macrophages, interstitial histiocytes [Fig. 23.14(a)], and
lymph nodes, especially hilar. Simple CWP is characterized
by 1-2 mm coal macules and larger coal nodules that have
a delicate collagen network [Fig. 23.14(b)]. These are found
predominantly in the upper lung lobes and the upper portions
of lower lobes. The macules and nodules of simple CWP
are typically adjacent to respiratory bronchioles. After many
years of simple CWP, black scars >2 cm in greatest dimension
herald the development of complicated CWP, that can be further
complicated by progressive massive fibrosis (PMF)
[Fig. 23.14(c)]. Microscopically, these black scars represent
carbon pigment and dense collagen, often with a region of
central necrosis. Most cases of simple CWP and mild complicated
CWP show normal pulmonary function tests. In a
minority of cases of complicated CWP, PMF leads to pulmonary
dysfunction, pulmonary hypertension (Chap. 26), and
cor pulmonale. Of note, once PMF has begun, it can progress
despite cessation of coal dust exposure.


What is silicosis? What is its epidemiological importance? What is it caused by and what are the types? What is its morphology and how does it progress? What is its pathophysiology? How are its lesions similar to CWP lesions? How are they different? What is it like microscopically? What are the nodules like when they develop in regional lymph nodes? What is like clinically? What can complicate it?

Silicosis, the most common chronic occupational disease
in the world, is caused by inhalation of silicon dioxide (silica),
which can be crystalline or amorphous. Crystalline silica
is much more fi brogenic than amorphous silica and exists
in the following forms: quartz (the most common), crystobalite,
and tridymite. Silicosis manifests as slowly progressive
nodular fi brosis developing after decades of exposure.
Pathogenetically, the SiOH groups on particle surfaces bind
to membrane proteins and phospholipids, leading to protein
denaturation and lipid damage. Exposure of macrophages to
silica can result in macrophage death or in macrophage activation
with release of numerous signaling molecules including
IL-1, TNF-α, fi bronectin, lipid mediators, oxygen-derived
free radicals, and fi brogenic cytokines. Similar to CWP, silicosis
lesions localize in the upper lung zones; in contrast, silicosis lesions are more fi brotic and less cellular than the
lesions of CWP. Early in the development of silicosis, small,
barely palpable, pale nodules appear in upper lung zones
[Fig. 23.15(a)]. With progression, these nodules coalesce into
hard, collagenous scars (silicotic nodules) [Fig. 23.15(b)] that
can undergo cavitation. Microscopically, the silicotic nodule
is composed of concentric layers of hyalinized collagen surrounded
by a dense collagen capsule [Fig. 23.15(c)]. The intervening
lung parenchyma can be compressed or overexpanded.
Silicotic nodules can also develop in regional lymph nodes,
where they typically undergo peripheral calcifi cation, imparting
an eggshell appearance radiographically. In some cases,
silicosis evolves into PMF. Clinically, presentation is usually
radiographic identifi cation of fi ne upper lung nodularity in an
asymptomatic worker, at which time pulmonary function tests are usually normal or near normal. If complicated by PMF,
there can be progression without additional silica exposure.
The relationship of silicosis to the development of lung cancer
in humans is controversial.


What is asbestos? What are the two types of fibers? What are they like? Which one is more common? Which one is more pathologic? Why? What diseases does asbestos cause?

Asbestos represents a family of crystalline hydrated silicates
that form fi bers of two general forms: serpentine chrysotile
fi bers, which are curly and fl exible, and amphibole fi bers,
which are straight, stiff, and brittle. Though less prevalent than
chrysotile fi bers, amphibole fi bers are more pathogenic, likely
due to aerodynamic properties that allow straight fi bers to align
in the airstream and be deposited more deeply in the lung.
Amphibole fi bers are less soluble than chrysotile fi bers, and so
chrysotile fi bers are leeched from tissue more quickly. Asbestos
shows activity as a tumor initiator and tumor promoter, in part
due to adsorption of toxic chemicals. Asbestos causes or contributes
to the development of many diseases, one of which—
asbestosis—is characterized by restrictive lung disease with
interstitial fi brosis. In addition to asbestosis, asbestos exposure is implicated
in the development of pleural plaques, pleural fi brosis,
pleural effusion, bronchogenic carcinoma, malignant
mesothelioma, and laryngeal and other extrapulmonary


What is the pathophysiology/morphology of asbestosis? How is it different from CWP and Silicosis? What is it like microscopically? What is it like clinically?

Asbestosis begins with inhalation of asbestos fi bers,
which impact and penetrate tissue at the bifurcation of small
airways and ducts. Subsequently, macrophages attempt to
ingest and clear the fi bers and release chemotactic and fi brogenic
mediators. Chronic fi ber deposition, causing persistent
mediator release, culminates in interstitial fi brosis and interstitial
infl ammation [Fig. 23.16(a), (b)]. The fi brosis begins
around respiratory bronchioles and alveolar ducts. Later
fi brosis extends into adjacent alveolar sacs and alveoli, with
progressive distortion of the architecture and eventual development
of a honeycomb appearance typical of many end-stage
chronic restrictive lung diseases. In addition to the interstitial
changes, asbestosis is typifi ed by fi brous thickening of
the visceral pleura, often leading to adhesions to the parietal
pleura with anchoring of the lung to the chest wall. In contrast to CWP and silicosis, the pathologic fi ndings in asbestosis
are more prominent in the lower lung zones but may extend
to the middle and upper zones. Microscopically, within the
interstitial fi brosis will be asbestos bodies, which are golden
brown and fusiform or beaded rods with a translucent core
[Fig. 23.16(c)]. Asbestos bodies are composed of an asbestos
fi ber coated with iron-containing, proteinaceous material.
Of note, other inorganic material may become coated with
similar iron-containing material. When seen outside the setting
of asbestos-related disease, such structures are called ferruginous
bodies, a less specifi c designation. Clinically, the
presentation of asbestosis is usually 10 to more than 20 years
after initial exposure and is characterized by dyspnea and productive
cough. Though asbestosis can remain static, it may
progress and lead to congestive heart failure, cor pulmonale,
and death.


What are pleural plaques? What is their morphology? What are they like clinically? How are they related to asbestos? What is the association b/w malignant mesothelioma and bronchogenic carcinoma and asbestos?

Pleural plaques (Fig. 23.17) are the most common
asbestos-related lesion and consist of a well-circumscribed
focus of dense collagen, often calcifi ed, on the parietal
pleura (usually posterolaterally and over the diaphragm).
Such plaques are a morphologic indication of asbestos
exposure but otherwise are clinically inconsequential.
Asbestos exposure increases the risk of malignant mesothelioma
~1,000-fold and increases the risk of bronchogenic
carcinoma fi vefold in nonsmokers and 55-fold among
smokers; mesothelioma and bronchogenic carcinoma are
discussed further in Chap. 31.


What does talcosis result from? What is it like morphologically?

Talcosis can result from inhalation of large amounts of talc,
a magnesium silicate used widely in industry and cosmetics. Morphologically, talcosis is characterized by granulomatous
infl ammation, hyaline nodules, and interstitial fi brosis (rarely
with PMF). Talc is highly birefringent when examined with
polarized light.


WWhat is berylliosis caused by? How is it characterized acutely? Chronically? What is it associated with?

Berylliosis is caused by exposure to airborne dusts or
fumes of metallic beryllium (atomic number 4) or its oxides
or salts, many of which are used in the electronics and aviation
industries. Acutely, berylliosis is characterized by acute
pneumonitis with DAD. Chronically, there is granulomatous infl ammation and interstitial fi brosis. Heavy beryllium exposure
is associated with bronchogenic carcinoma (Chap. 31).


What are the hard metal diseases? How are they caused? What are they characterized by? What is Welder's pneumoconiosis associated with and what is it like morphologically?

Additional pneumoconioses include the hard metal
diseases that are associated with tungsten carbide and
cobalt exposure and characterized by giant cell interstitial
pneumonitis. Welder’s pneumoconiosis is most often associated
with oxides of aluminum, iron, titanium, or manganese,
and patients may show varying degrees of interstitial
fi brosis depending on the specific metal oxide involved.