Interstitial lung diseases are a heterogeneous group of conditions that involve the lung parenchyma. They are characteristically diffuse and infiltrative in nature, involving the peribronchovascular interstitium of the lung, although alveolar involvement may occur as well. The author addresses the clinical and radiographic findings of each of these dieseases. The organization of these diseases into a structural framework facilitates understanding of their histologic and radiographic findings, and increases the likelihood that an accurate diagnosis will be made.
Dr. Gotway is an Assistant Professor of Radiology at the
University of California, San Francisco and Chief of Thoracic
Imaging at San Francisco General Hospital, San Francisco,
Interstitial lung diseases (ILDs) are a heterogeneous group of
conditions that involve the lung parenchyma. These entities are
characteristically diffuse and infiltrative in nature, involving
the peribronchovascular interstitium of the lung, although alveolar
involvement may occur as well. ILDs are not malignant or infectious
in etiology, although they may cause significant morbidity and
mortality. The precise causes of most ILDs are unknown. They are
grouped together because they share similar clinical, radiographic,
physiologic, and/or pathologic manifestations.
Various approaches have been used to classify this heterogeneous
group of disorders, and none are very satisfying.
In the following classification scheme, certain disorders are
grouped together because of a common pathologic finding or a shared
radiographic abnormality. Because numerous ILDs exist, it is
inevitable that no classification scheme will satisfactorily
categorize them with complete accuracy. For purposes of
organization, in broad terms, they may be grouped as follows:
1) interstitial pneumonias (IPs):
a) usual interstitial pneumonia,
b) non-specific interstitial pneumonitis,
c) acute interstitial pneumonia,
d) alveolar macrophage pneumonia (formerly called desquamative
e) bronchiolitis obliterans organizing pneumonia;
2) diffuse infiltrative disease characterized by granulomas:
b) hypersensitivity pneumonitis;
3) lymphocytic interstitial pneumonia (LIP);
5) ILD characterized by cysts (Langerhans' cell histiocytosis,
6) disorders characterized by interlobular septal
a) pulmonary lymphangitic carcinomatosis,
b) pulmonary edema, and
c) pulmonary alveolar proteinosis;
7) eosinophilic syndromes;
8) pulmonary hemorrhage syndromes;
The diagnosis of these entities rests on integration of
clinical, physiologic, and radiologic information. Frequently, a
tissue diagnosis is required for definitive diagnosis. For some of
the conditions, flexible fiberoptic bronchoscopy with
bronchoalveolar lavage and transbronchial biopsy may suffice, but
surgical lung biopsy is often required. A complete description of
the above classification scheme of diffuse lung disease is beyond
the scope of this article. We will instead focus on the IPs and
several other diffuse lung diseases that may have characteristic
high resolution computed tomography (HRCT) appearances:
hypersensitivity pneumonitis, Langerhans cell histiocytosis, and
lymphangiomyomatosis. Several authoritative texts and excellent
review articles are available for a more complete discussion the
imaging of diffuse lung diseases.
initially classified IPs into 5 types based on their histologic
1) usual interstitial pneumonia (UIP);
2) desquamative interstitial pneumonia (DIP);
3) giant cell interstitial pneumonia (GIP);
4) lymphocytic interstitial pneumonia (LIP); and
5) bronchiolitis obliterans interstitial pneumonia (BIP).
These entities do not represent diseases per se; rather, they
represent fundamental responses of the lungs to injury or a
pathologic condition. Each of the IPs may be seen in association
with several different diseases; conversely, several IPs may be
seen in the same patient.
Recently, IPs have been reclassified.
The current pathologic classification of the IPs includes:
2) nonspecific interstitial pneumonitis (NSIP);
3) acute interstitial pneumonia (AIP);
4) alveolar macrophage pneumonia (AMP, which was previously
known as DIP); and
5) bronchiolitis obliterans organizing pneumonia (BOOP).
LIP is no longer believed to represent an interstitial
pneumonia. It is now thought to be a potentially malignant
lymphoproliferative pulmonary disorder. GIP is now believed to be a
hard metal pneumoconiosis, and is no longer considered among the
IPs. The above classification scheme is commonly employed in the
radiographic (chest radiograph, HRCT) approach to patients with
Usual interstitial pneumonia
Histologic findings--UIP is the most common IP.
In the United Kingdon, UIP is known as cryptogenic fibrosing
alveolitis. Pathologically, at low power magnification, UIP is
characterized by areas of normal lung alternating with regions of
interstitial inflammation, fibrosis, and honeycombing.
Findings are predominantly subpleural. At higher power, the
interstitial inflammation is seen to consist of lymphocytic and
plasma cell infiltration within alveolar septa. Proliferating
fibroblasts (fibroblastic foci) and dense collagen deposition are
seen, as is hyperplasia of type 2 pneumocytes. These changes
represent a response of the lung to injury, and are not specific to
UIP. The simultaneous presence of multifocal areas of active
inflammation, fibroblastic proliferation, and fibrosis interspersed
with normal lung parenchyma ("temporal variegation") is the
histologic hallmark of UIP.
The above pathologic pattern of UIP refers to a histologic
abnormality. The clinical syndrome that is most commonly associated
with this histologic pattern is idiopathic pulmonary fibrosis
(IPF). Other conditions in which a UIP-like histologic pattern may
be encountered include connective tissue diseases (such as
rheumatoid arthritis and scleroderma), pneumoconiosis (particularly
asbestosis), radiation injury, chronic aspiration, end-stage
hypersensitivity pneumonitis, and drug reactions (e.g.,
nitrofurantoin). Because there may be other characteristic
histopathologic features present in these other syndromes, the term
UIP is best reserved for cases in which UIP histology is present
but not associated with another condition; i.e., for patients with
Idiopathic pulmonary fibrosis
Clinical features--Patients with idiopathic pulmonary fibrosis
(IPF) are typically aged 50 to 70 years, and men are more commonly
affected than women.
Typical symptoms include dry cough and dyspnea on exertion.
Physical exam may reveal "velcro-type" inspiratory crackles, and
digital clubbing may be found in 25% to 50% of cases. Chest pain
and hemoptysis are uncommon. Laboratory investigations are
generally unrevealing. Pulmonary function tests (PFTs) commonly
reveal a restrictive defect, with decreased total lung capacity,
functional residual capacity, and residual volume.
The diffusing capacity of carbon monoxide (DLCO) is commonly
reduced as well. Overall survival is poor, with a 30% to 50% 5-year
survival rate. Treatment is often ineffective (<10% of patients
will respond), and generally relies on the use of corticosteroids
and immunosuppressive/cytotoxic agents. Single lung transplantation
may be considered in selected patients.
Radiographic findingsChest radiographs: Plain chest
radiographs typically show decreased lung volumes and bilateral,
basilar and subpleural predominant reticulation and honeycombing
Serial radiographs are particularly helpful in revealing slowly
diminishing lung volumes over time.
A ground glass appearance is uncommonly encountered, but is also
typically basilar in distribution.
Small nodules are uncommonly seen, and radiographs are normal in
less than 10% to 15% of cases.
The severity of findings on the plain chest radiograph correlates
poorly with the clinical functional status.
HRCT: HRCT commonly reveals patchy, basilar and subpleural
irregular linear opacities (intralobular, interstitial thickening),
characteristically associated with traction bronchiectasis and
honeycombing (figure 2).
Ground glass opacity may be encountered, and presumably reflects
alveolitis and may indicate treatable disease.
However, ground glass opacity has been shown to correlate with
alveolar septal granulation tissue and fibrosis histologically,
raising the possibility that ground glass opacity may actually
reflect early lung fibrosis, but not necessarily reversible
When ground glass opacity is seen among other findings of fibrosis
(reticular opacities, traction bronchiectasis, and honeycombing),
the ground glass opacity likely represents fibrosis below the limit
of resolution of HRCT. Ground glass opacity should be interpreted
as potentially treatable disease only when there are no associated
HRCT findings of fibrosis.
Fibrosis initially appears as fine reticular opacities; these
reticular opacities become coarser as the disease progresses.
Discrete nodules are seen occasionally. Irregular interlobular
septal thickening may be present as well. Mild mediastinal lymph
node enlargement is common, but lymph node enlargement in >2 cm
Several studies have shown that CT and HRCT are superior to
plain chest radiographs for the assessment of patients with IPF.
For example, honeycombing may be seen in up to 90% of CT studies as
compared with 30% of cases on plain radiographs. HRCT findings have
been shown to correlate with symptoms and pulmonary function
abnormalities in patients with IPF.
HRCT allows a distinction of active, potentially reversible
alveolitis from irreversible fibrosis in the majority of patients
with IPF, obviating the need for surgical biopsy in characteristic
HRCT can be helpful in predicting potential response to treatment
and long-term prognosis in patients with IPF.
HRCT is also useful for directing the optimal site for lung biopsy
in difficult cases.
Generally, biopsy is directed away from regions of obvious
honeycombing and toward regions of ground glass opacity.
Nonspecific interstitial pneumonitis
NSIP refers to interstitial pneumonia that cannot be classified
into the known patterns of UIP, AIP, DIP, or BOOP. Some have
considered NSIP a wastebasket diagnosis. However, because these
patients may have a better prognosis than patients with IPF and
treatment strategies are different for NSIP than for causes of UIP,
NSIP has been classified separately from other forms of
Histologic features--Pathologically, NSIP is characterized by
varying degrees of inflammation and fibrosis within the walls of
Although the process may be patchy (with areas of normal lung
interspersed), the histologic abnormalities are temporally uniform,
unlike the temporal variegation characteristic of UIP histology.
NSIP histology has been further subdivided into types I, II, and
III depending on the degree of associated fibrosis. Type I NSIP
consists of interstitial inflammation without fibrosis, type II
NSIP by interstitial inflammation with roughly equal amounts of
fibrosis, and type III NSIP by interstitial collagen deposition
with minimal interstitial inflammation.
Like UIP, the histologic lesion of NSIP may be associated with
certain clinical syndromes, such as connective tissue diseases,
hypersensitivity pneumonitis, and organic dust or other exposures.
Clinical findings--Clinically, the most common presenting
complaint is dyspnea. A non-productive cough may occur. The mean
duration of symptoms is usually shorter with NSIP (months) than IPF
Radiographic findingsChest radiographs: Radiographically, NSIP
may be difficult to distinguish from causes of UIP. Reticular and
patchy areas ground glass opacities with a basilar, subpleural
predominance are commonly encountered (figure 3).
Findings may closely resemble cases of UIP. Air space consolidation
may also be seen. Lung volumes may be maintained if the lesion of
NSIP is not associated with fibrosis.
HRCT: HRCT scan findings include basilar, subpleural reticular
opacities consistent with intralobular interstitial thickening.
Ground glass opacity is commonly seen and suggests active,
treatable alveolitis when seen in the absence of discrete
honeycombing (figure 4). Bronchial dilation may be seen in areas of
ground glass opacity; this finding generally correlates with
greater amounts of fibrosis histologically (Type III NSIP).
Honeycombing is rarely encountered, and generally suggests the
diagnosis of UIP-related diseases as opposed to NSIP. It has been
shown that the ground glass opacity seen with NSIP may improve
markedly with treatment (figure 5), unlike UIP-related illnesses.
Although some investigators have shown that ground glass opacity
may evolve into linear and reticular opacities with honeycombing on
follow-up HRCT, it is unclear if untreated NSIP inexorably
progresses to honeycomb lung. The extent of improvement of
abnormalities on HRCT have been shown to correlate with functional
improvement following treatment.
Acute interstitial pneumonia
Histologic features--Acute interstitial pneumonia (AIP) was
previously known as Hamman-Rich syndrome.
Pathologically, AIP is characterized by diffuse alveolar damage
with hyaline membrane formation and alveolar wall edema during the
acute, exudative phase (up to day 6). Later, fibroblast
proliferation supervenes in the subacute proliferative phase (day 4
Vascular thrombosis may also occur. Finally, after day 8, the
chronic, fibrotic phase characterized by traction bronchiectasis
and fibrosis may occur.
Clinical findings--AIP is characterized by the abrupt onset of
respiratory failure requiring mechanical ventilation in a
previously healthy individual.
Antecedent histories variously include cough, fever, and shortness
of breath. AIP may be thought of as ARDS without a known cause.
The mortality is high (60% to 100%), and significant parenchymal
opacities on chest radiography and CT may occur in survivors.
Radiographic findingsChest radiographs: Findings on plain
radiographs include bilateral, symmetric ground glass opacities and
foci of air space consolidation (figure 5). In some patients,
subpleural reticulation and honeycomb lung may occur.
HRCT: The findings of AIP on HRCT have been described
and correlated with the pathologic stage of disease.
Predictably, bilateral, roughly symmetric areas of ground glass
opacity and air space consolidation are encountered, often
associated with interlobular septal thickening (figure 6). Traction
bronchiectasis and architectural distortion may be seen,
particularly in the proliferative subacute and chronic fibrotic
phase. AIP is characterized by its rapid time course.
Alveolar macrophage pneumonia (AMP), previously known as
desquamative interstitial pneumonia (DIP) and respiratory
bronchiolitis-interstitial lung disease (RB-ILD)
Histologic features--Desquamative interstitial pneumonia has
recently been renamed alveolar macrophage pneumonia.
AMP (DIP) is now considered to be primarily a smoking-related
AMP (DIP) may represent the most severe manifestation of
smoking-related changes of the small airways and lung parenchyma.
At the mild end of the spectrum of airway-related changes secondary
to cigarette smoke is respiratory bronchiolitis; respiratory
bronchiolitis-associated interstitial lung disease represents more
severe airway inflammation due to cigarette smoke,
with limited amounts of peribronchiolar inflammation accompanying
alveolar macrophage accumulation. The characteristic histologic
finding of AMP (DIP) is alveolar accumulation of macrophages.
Minimal inflammatory cell infiltration and fibrosis may also be
present. AMP (DIP) is distinguished from UIP by the fact that the
former is a temporally uniform process that is not accompanied by
fibroblastic foci, unlike UIP. Also, macrophage accumulation in AMP
(DIP) is diffuse, whereas in UIP, it is focal. AMP (DIP) used to be
thought of as early stage UIP, but the two are now considered to be
Clinical findings--AMP (DIP) is essentially a rare disease of
smokers. The peak incidence occurs in patients 30 to 50 years of
age. Most patients present with dyspnea. In general, symptoms are
more acute with DIP than with UIP. Pulmonary function testing may
reveal a restrictive pattern with decreased diffusing capacity.
Hypoxemia may be present. PFT abnormalities tend to be less severe
than patients with UIP. The prognosis for patients with AMP (DIP)
is quite favorable. The 10-year survival is about 70%.
RB-ILD is also a disease of heavy smokers. These patients
typically have shortness of breath and cough. The prognosis of
RB-ILD is excellent. Progression to end-stage lung fibrosis does
Radiographic findingsChest radiographs: The chest radiograph
in cases of AMP (DIP) may reveal ground glass opacity or air space
consolidation, particularly in a basilar and subpleural
distribution (figure 7).
Patients with AMP (DIP) are more likely to demonstrate ground glass
opacity than patients with UIP. Irregular linear opacities, often
lower lung predominant, may also be seen. Nodules, adenopathy, and
effusion are all uncommon. A normal chest radiograph has been
reported in 3% to 22% cases.
The chest radiograph in RB-ILD typically demonstrates bilateral,
mid and lower lung predominant linear and reticular opacities,
frequently associated with bronchial wall thickening. Honeycombing
is not present (figure 8).
HRCT: HRCT findings of AMP (DIP) include basilar, subpleural,
lower lobe predominant ground glass opacity and irregular reticular
opacities (figure 9).
Although the spectrum of findings of AMP (DIP) and UIP overlap,
ground glass opacity is more commonly seen with AMP (DIP) than UIP.
Up to half of patients with AMP (DIP) may show reticulation,
and honeycombing may be seen in 30%. Compared to UIP, findings that
suggest fibrosis are relatively mild.
The HRCT findings of AMP (DIP) may improve with treatment.
HRCT findings of RB-ILD typically include patchy areas of ground
glass opacity, perhaps accompanied by airway thickening (figure
10). Nodules, interlobular septal thickening, effusions, and
adenopathy are uncommon.
Bronchiolitis obliterans organizing pneumonia
Histologic features--Idiopathic bronchiolitis obliterans
organizing pneumonia (BOOP), also known as cryptogenic organizing
pneumonia (COP) in the United Kingdom, is a disease characterized
by granulation tissue polyps within the lumina of bronchioles and
alveolar ducts and patchy areas of organizing pneumonia.
Fibrosis and inflammation are not conspicuous features of BOOP.
BOOP may be idiopathic (cryptogenic organizing pneumonia), although
a BOOP-like reaction may be seen with pulmonary infections, drug
reactions, as a complication of organ transplantation, collagen
vascular disease, Wegener's granulomatosis, and following toxic
Clinical findings--Patients with idiopathic BOOP typically
present with a several month history of non-productive cough.
Most patients report symptoms being present for <6 months.
Low grade fevers, malaise, and shortness of breath are also seen.
The presentation has been characterized as "flu-like" in 40% of
patients. PFTs typically reveal a restrictive defect. The prognosis
of idiopathic BOOP is good; patients usually respond to
Radiographic findings--Chest radiographs: The characteristic
chest radiographic features of idiopathic BOOP include bilateral,
patchy, nonsegmental areas of air space consolidation and/or ground
A peripheral distribution is characteristic, although not seen in
the majority of patients (14%) (figure 11).
Recurrent/migratory opacities, often in the upper lobe, have been
reported. Small nodules may be present, most commonly accompanying
air space consolidation. Irregular linear opacities are less common
and generally are not dominant features on the radiograph. Pleural
effusions are also uncommon. Adenopathy and honeycomb cysts are
CT and HRCT: CT and HRCT scans in BOOP may demonstrate:
1) patchy air space consolidation (80%) or ground glass opacity
(60%), often with a subpleural (50% to 60%) and/or peribronchiolar
distribution. No particular zonal predilection is present (figures
12 and 13);
2) small ill-defined nodules have been reported in 30% to 50% of
cases, and may be peribronchiolar in distribution;
3) bronchial wall thickening and bronchial wall dilation have
also been described; and
4) irregular, large nodules or masses.
Irregular linear opacities, pleural effusions, and adenopathy
may variously be seen, but are generally less common. HRCT provides
useful information for guiding surgical biopsy.
Most patients respond well to treatment (figure 13), although
relapses do occur and a small minority of patients may even die due
to respiratory failure.
Interstitial lung diseases characterized by granulomas:
Hypersensitivity pneumonitis (HP), also known as extrinsic
allergic alveolitis in the United Kingdom, is an allergic lung
disease that results from the inhalation of antigens contained in a
variety of organic dusts. Farmer's lung, the most well known HP
syndrome, results from the inhalation of fungal organisms
(thermophilic actinomycetes) that grow in moist hay. Many other HP
syndromes also result from exposure to fungi, and they are usually
named after the setting in which the exposure occurs or the organic
Pathologic features--HP is characterized by interstitial
alveolitis, cellular bronchiolitis, and noncaseating epitheloid
The diagnosis of HP is confirmed by the presence of all three of
these findings, but all three are not invariably present. Thus, the
diagnosis often rests on a combination of the proper clinical
scenario, characteristic radiographic findings, and suggestive
histopathologic findings. The radiographic and pathologic findings
in the various etiologies of HP are similar, thus the disease may
be classified into acute, subacute, and chronic stages regardless
of the responsible antigen.
Clinical findings--An acute, heavy exposure to an offending
antigen may produce fever, chills, dry cough, and dyspnea.
Long-term exposure can produce shortness of breath with few or
minimal systemic symptoms. Recurrent exposure may result in
recurrent acute episodes, possibly superimposed on chronic changes.
Chronic HP may present with progressive respiratory impairment. It
is not uncommon that, despite extensive questioning, a history of
an exposure to an offending antigen cannot be elicited. Thus, a
tissue diagnosis is frequently required.
Radiographic findingsChest radiographs: In the acute stage,
heavy exposure to an enticing antigen may result in ill-defined,
bilateral air space disease. These findings reflect alveolar
inflammation due to neutrophils, eosinophils, lymphocytes, and
large mononuclear cells and/or obstructive pneumonitis. Patients
are rarely seen at this stage.
The acute phase may resolve in several days. Then, in the
subacute phase, a fine nodular pattern may develop on the chest
radiograph (figure 14). The nodular pattern correlates with
alveolitis; interstitial infiltration; small, poorly defined
granulomas; and cellular bronchiolitis. These histologic findings
are usually most apparent in a peribronchiolar distribution. The
classic radiographic appearance of HP is recurrent, transient areas
of consolidation superimposed on a fine, nodular pattern. In the
majority of patients, however, the chest radiograph is normal.
The subacute presentation may be seen following a heavy acute
exposure or with repeated, low-level exposures.
In the chronic phase, fibrosis develops months or years
following the initial exposure. The fibrosis can be patchy in
distribution, often with a mid-lung predominance.
HRCT: HRCT findings in the acute phase of HP include bilateral
air space consolidation and small, (1 to 3 mm diameter) ill-defined
Patients are uncommonly imaged in this phase.
HRCT findings of HP in the subacute phase include ground glass
opacities with poorly defined centrilobular nodules.
Occasionally, the poorly defined centrilobular nodules may be the
predominant finding (figure 15). HP centrilobular nodules are
commonly mid- and lower-lung predominant, although a diffuse
distribution may occur. Acute and subacute HP may be very difficult
to distinguish from DIP. Centrilobular nodules favor diagnosis of
the latter. Areas of decreased lung attenuation on inspiratory HRCT
images (mosaic perfusion) may be seen in subacute HP, and air
trapping may be demonstrated on postexpiratory scans.
In a few cases, air trapping on postexpiratory scans may be the
only finding of HP (figure 16).
Occasionally the finding of ground glass opacity, normal lung, and
mosaic perfusion on the same inspiratory scan image (the
"headcheese" sign) may reflect the combination of alveolitis and
air flow obstruction that characterize this disease (figure 17).
Chronic HP is characterized by fibrosis on HRCT (figures 18 and
19), although the findings of active disease may be superimposed.
Fibrosis in HP often shows a mid-lung predominance, although the
findings may be distributed evenly throughout the upper, mid, and
Relative sparing of the lung bases, seen in a majority of cases of
chronic HP, may allow chronic HP and UIP to be distinguished
The headcheese sign (figure 19) may be seen in chronic HP also.
HRCT is more sensitive than chest radiographs in the assessment of
patients with HP,
although the sensitivity of HRCT is not 100%.
Sarcoidosis may also be considered as an interstitial lung
disease characterized by granulomas. The clinical and radiographic
features of sarcoidosis have been described extensively elsewhere
and will not be considered further here.
Although early in its course, granulomas may be seen
histologically, the radiographic presentation (in particular the
HRCT manifestations) of Langerhans cell histiocytosis are dominated
by pulmonary cysts. Thus, this disorder will be considered under
ILDs characterized by cyst formation.
Interstitial lung diseases characterized by cyst
formation: Langerhans' cell histiocytosis
Histologic features--Langerhans' cell histiocytosis, also known
as histiocytosis X or eosinophilic granuloma of the lung (EG), is
an idiopathic disease of the lung characterized in its early stages
by granulomatous nodules containing Langerhans' histiocytes and
eosinophils, which are primarily peribronchial in distribution. In
its later stages, the cellular granulomas are replaced by fibrosis
and the formation of cysts.
Clinical findings--EG is an uncommon condition. The majority of
patients with EG are young or middle-aged adults (average age of
presentation is 32 years). Affected patients present with
nonspecific symptoms such as cough, dyspnea, chest pain, weight
loss, and fever.
The physical examination is usually normal, and routine laboratory
measurements are usually not helpful.
Up to 20% of patients present with pneumothorax. There is a slight
male predominance, and more than 90% of patients are smokers.
A causal relationship with smoking is likely.
A diminished DLCO is common,
with varying degrees of restriction and airflow obstruction also
Radiographic findingsChest radiographs: The radiographic
findings consist of reticular, nodular, reticulonodular, and cystic
disease, often in combination. Abnormalities are usually bilateral,
involving predominately the middle and upper lung zones with
relative sparing of the costophrenic angles (figure 20). Lung
volumes are characteristically normal or increased.
HRCT: Cystic air spaces, which are usually <10 mm in
diameter, are typically seen on HRCT. The lung cysts have walls up
to several millimeters thick. The presence of distinct walls allows
differentiation of these cysts from areas of emphysema, which can
also be seen in some patients. Although many cysts appear round,
they can also have bizarre shapes, appearing bilobed, clover-leaf
shaped, or branching (figure 21). An upper-lobe predominance of
cysts is common; the lung bases and the costophrenic sulci are
relatively spared. In some patients, cysts are the only abnormality
visible on HRCT, but in the majority of cases, small nodules
(usually <5 mm in diameter) are also present (figure 21). The
nodules are usually solid in appearance, but larger nodules
(approximately 1 cm in diameter) sometimes show lucent centers,
presumably corresponding to small 'cavities' (figure 21).
These cavitating nodules may eventually evolve into cysts.
In many patients with cysts or nodules, the intervening lung
parenchyma appears normal on HRCT, without evidence of fibrosis or
Mediastinal adenopathy in EG has been reported.
The findings of EG may stabilize or even regress with smoking
although recrudescence has also been observed.
Interstitial lung diseases characterized by cyst
Histologic features--Lymphangiomyomatosis (LAM) is a rare
disease characterized by progressive proliferation of spindle
cells, resembling immature smooth muscle, in the lung parenchyma
and along lymphatic vessels in the chest and abdomen. Proliferation
of spindle cells along the bronchioles leads to air trapping and
the development of emphysema and thin-walled lung cysts. Rupture of
these cysts can result in pneumothorax. The spindle cell
proliferation can also involve the hilar, mediastinal, and
extrathoracic lymph nodes, sometimes resulting in dilation of
intrapulmonary lymphatics and the thoracic duct. Involvement of the
lymphatics can lead to chylous pleural effusion. Proliferation of
cells in the walls of pulmonary veins may cause venous obstruction
and lead to pulmonary hemorrhage.
Clinical findings--The majority of patients present with
dyspnea. Sixty percent develop chylous pleural effusions; 40%
and 30% to 40% develop blood-streaked sputum or frank hemoptysis.
Almost all patients die within 10 years of the onset of symptoms.
Recently, improved prognosis has been reported following treatment
with progesterone or oophorectomy.
Lymphangiomyomatosis essentially occurs only in women of
child-bearing age, usually between 17 and 50 years old.
Rarely, however, it may be seen in postmenopausal women; the oldest
patient described was 69 years of age. Caucasians are more commonly
affected than other racial groups. Identical clinical, radiologic,
and pathologic pulmonary changes may be seen in about 1% of
patients with tuberous sclerosis.
Although tuberous sclerosis affects both sexes equally, the
pulmonary changes have been described almost exclusively in
Radiographic findings--Chest radiographs: The plain radiologic
manifestations of LAM include reticular, miliary, and honeycomb
patterns (figure 22). Lung volumes can be increased in patients
with this disease. The radiologic findings may precede, accompany,
or postdate other manifestations of the disease such as
pneumothorax and chylous pleural effusion.
In patients treated for recurrent pneumothoraces, extensive
parenchymal abnormalities not visible on radiographs have been
demonstrated at surgery.
HRCT: On HRCT, patients with LAM characteristically show
numerous thin-walled cysts, surrounded by relatively normal lung
parenchyma (figure 23). These cysts usually range from 2 to 5 mm in
diameter, but can be larger. Their size tends to increase with
progression of the disease. Irregularly shaped lung cysts, as are
seen in patients with EG, are uncommon.
In the majority of patients, the cysts are distributed diffusely
throughout the lungs and no lung is spared; diffuse lung
involvement is seen even in patients with mild disease. In most
patients, the lung parenchyma between cysts appears normal on HRCT.
Small nodules are occasionally seen, but are not a prominent
feature of this disease as they are with EG.
Other features of LAM, which can be seen on HRCT, include hilar,
mediastinal, and retrocrural adenopathy.
Pleural effusion can also be seen, and is helpful in distinguishing
LAM from EG.
Although no classification scheme is entirely satisfying, the
interstitial lung diseases may be broadly grouped into categories
based on common clinical, radiographic, or histologic findings. The
radiographic findings are usually nonspecific, HRCT findings may
narrow the differential diagnosis and occasionally allow a specific
diagnosis to be made. Organization of these diseases into a
structural framework facilitates understanding of their histologic
and radiographic findings, and increases the likelihood that an
accurate diagnosis will be made. AR