Chest Radio 17 Diffuse Fine Nodular Opacities

17 DIFFUSE FINE NODULAR OPACITIES
Fig. 17.1
235
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236 PART 2 Pulmonary Opacities
Fig. 17.2
QUESTIONS
1. Based on the radiologic appearance of the case illustrated in Fig. 17.1, which one of
the following diagnoses is the most urgent one?
a. Miliary tuberculosis.
b. Silicosis.
c. Langerhans cell histiocytosis.
d. Hypersensitivity pneumonitis.
e. Sarcoidosis.
2. Regarding Fig. 17.2, which of the following is the most likely diagnosis?
a. Sarcoidosis.
b. Metastatic carcinoma.
c. Langerhans cell histiocytosis.
d. Hypersensitivity pneumonitis.
e. Histoplasmosis.
Mark the following questions True or False:

3. ______ Sarcoidosis and silicosis may present with the pattern seen in Fig. 17.1 in
combination with hilar adenopathy.
4. _ _____ Bronchoscopy with biopsy is contraindicated in the evaluation of patients in

whom the pattern is believed to be secondary to tuberculosis.

CHAPTER 17 Diffuse Fine Nodular Opacities 237
Chart 17.1 DIFFUSE FINE NODULAR OPACITIES
I. Infections
A. Tuberculosis41,235,288
B. Fungus infections (histoplasmosis,97 blastomycosis,450,561 coccidioidomycosis373),
Aspergillosis (rare),46 cryptococcosis (rare)200,252,321
C. Bacterial infections (bronchopneumonia—unusual early presentation),
nocardiosis208
D. Viral pneumonia (e.g., varicella)382,451,599
II. Environmental diseases
A. Silicosis and coal workers’ pneumoconiosis80,86,429
B. Berylliosis80,175
C. Siderosis80,175
D. Hypersensitivity pneumonitis or allergic alveolitis (farmer’s lung)353,497,570
E. Hard metal pneumoconiosis299
III. Langerhans cell histiocytosis1,585
III. Sarcoidosis86,103,407
VIII. Metastatic tumor175
A. Thyroid carcinoma
B. Melanoma76
C. Other adenocarcinomas (e.g., gastrointestinal tumors)
IX. Other
A. Alveolar microlithiasis (rare)467
B. Gaucher disease645
C. Granulomatosis with polyangiitis (rare)
D. Immunotherapy (bacillus Calmette-Guérin)272
Discussion
Detection of very small nodules is a serious challenge for the radiologist. Nodules mea-
suring 1 to 3 mm (see Fig. 17.1) are marginally detectable on the chest radiograph
and may require high-resolution computed tomography (HRCT) for confirmation (Fig.
17.3, A and B). Examination of gross specimens often reveals many more nodules of a
much smaller size than can be resolved as separate opacities on the chest radiograph.
Heitzman suggested that miliary nodules are probably seen on the radiograph because
of the effect of summation—that is, a “stacked coin effect.”235 These very small nodules
are sometimes more easily appreciated on the posteroanterior view in the costophrenic
angle and on the lateral view in the retrosternal clear space. Furthermore, small nodu-
lar opacities may occasionally be confused with very small pulmonary vessels seen on
end. This mistake is usually avoided by identifying an associated, branching vascular
pattern around the nodule. Also, miliary nodules are typically much more diffuse than
the fine nodular appearance created by normal vessels.
The sharpness of the borders of the nodules is an important criterion for narrowing
the differential. Small opacities may be caused by small, sharply defined interstitial
nodules or by minimal involvement of the distal air spaces, which results in ill-defined
opacities with an acinar pattern.175,601 This distinction is the key to limiting the dif-
ferential. If the pattern includes small, fluffy, or ill-defined opacities, then alveolar
edema, exudate, or hemorrhage should be considered. The presence of ill-defined bor-
ders should prompt examination of the radiograph for other signs of air space filling
disease (see Chapter 15). In contrast, the pattern of very small but sharply defined or
discrete opacities should reassure the radiologist that the nodules are more likely inter-
stitial and are thus associated with one of the entities listed in Chart 17.1.
B
Fig. 17.3 A, Posteroanterior chest radiograph of a patient treated for acute myeloid leukemia with a
bone marrow transplant demonstrates increased opacities that are suggestive of diffuse small nodules.
B, High-resolution computed tomography confirms a random distribution of small nodules suggesting
miliary tuberculosis, and transbronchial biopsy confirmed the diagnosis.
Miliary nodules are usually 1 or 2 mm in diameter and not more than 3 mm,221,601
but size should rarely influence the differential diagnosis because all of the entities listed
in Chart 17.1 may produce larger nodules (i.e., up to 3 to 4 mm). It is true, however, that
the size of the nodules does occasionally influence the radiologist to favor some mem-
bers of the differential list over others. For example, the small nodules of Langerhans cell
histiocytosis are rarely as small as 1 or 2 mm. Although the very small nodular pattern
does not eliminate Langerhans cell histiocytosis from the differential, it makes other
diagnoses, such as sarcoidosis, more likely. Very small nodules mixed with larger nodules
should not be described as miliary and are more likely to be a clue to suspect metastatic
tumor. Because these small nodules usually have no distinguishing features, the radiolo-
gist must search for associated radiologic and clinical findings to narrow the differential.
INFECTIOUS DISEASES
Miliary tuberculosis (see Fig. 17.1) results from hematogenous dissemination and
almost invariably leads to a dramatic febrile response with night sweats and chills.
Exceptions to this clinical presentation are probably the result of altered immune
response and are most commonly encountered in older adults, patients receiving ste-
roids or chemotherapy, and patients in the late stages of AIDS with a very low CD 4
count. It must be emphasized that bacteriologic confirmation of miliary tuberculosis
is not always easily obtained. Despite the disseminated disease, the miliary nodules
are interstitial. Sputum cultures may continue to be negative in the face of miliary
tuberculosis because the organisms are primarily in the interstitium rather than in
the air spaces. More invasive procedures, such as bronchoscopy with transbronchial
biopsy, may be required to confirm the diagnosis (answer to question 4 is False). Mili-
ary tuberculosis has a high mortality rate, which requires prompt diagnosis and treat-
ment (answer to question 1 is a).
Any of the fungal infections listed in Chart 17.1 may mimic the radiologic appear-
ance of miliary tuberculosis, but this pattern is most commonly the result of histoplas-
mosis, coccidioidomycosis, or North American blastomycosis. The clinical response to
these fungal infections may be more varied than to tuberculosis. For example, some
patients have a profound systemic response leading to death, others have a mild, influ-
enza-like syndrome, and a few are minimally symptomatic. In the last instance, the
radiologic abnormality may be more impressive than the clinical course. A history of
exposure to a specific fungus is occasionally obtained. For example, history of a trip
to the desert virtually confirms the diagnosis of coccidioidomycosis, whereas exposure
to soil contaminated with bird or chicken droppings in the Ohio River Valley strongly
suggests histoplasmosis. Such histories also suggest that the nodules are not always
the result of hematogenous dissemination, such as in miliary tuberculosis, but may
also be due to an inhaled organism. This difference in cause helps explain some of the
clinical and radiologic differences in the two conditions. The acute epidemic form of
histoplasmosis produces the radiologic appearance of larger, ill-defined nodules, simi-
lar to that of bronchopneumonia (see Chapter 16). As the patient recovers, the nodules
may regress in size and become more sharply defined and may even begin to calcify
(Fig. 17.4). Therefore, the fine nodular pattern may represent acute hematogenous
dissemination of the fungi or the healed phase of the disease. Some patients with
histoplasmosis who develop this diffuse nodular pattern are later observed to develop
diffuse, small, calcified nodules (answer to question 2 is e). Numerous calcified nodules
are virtually diagnostic of histoplasmosis, especially when associated with hilar lymph
node or splenic calcifications.
Bacterial infections generally do not produce this fine nodular pattern of pulmo-
nary involvement. However, there are occasional reports of early bacterial pneumonias
leading to this pattern. Nocardia, previously regarded as a fungus, is now considered to
be a gram-positive bacterium that rarely causes infection in normal patients but is an
opportunistic infection in patients who are immunosuppressed. Nocardia may produce
a variety of pulmonary patterns, including miliary nodules.208,467
Viral pneumonia, especially varicella or chickenpox pneumonia, may result in
fine nodules.382 The nodules represent localized collections of inflammatory cells.
When the course of the illness is severe, the pattern may be transient and rapidly
Fig. 17.4 The small nodules seen in this case of histoplasmosis are more circumscribed than expected
with miliary spread of infection and likely indicate that the patient has recovered from a transbronchial
infection.
followed by larger, multifocal, ill-defined opacities or even diffuse coalescent opacities

and is complicated by adult respiratory distress syndrome. Such a course is frequently
encountered in patients who are immunosuppressed. As with histoplasmosis, the small
nodules caused by varicella pneumonia may heal with the development of multiple,
calcified nodules. However, confirmation of this cause of the calcified nodules may be
virtually impossible unless the diagnosis of varicella pneumonia is established in the
acute phase of illness. Clinical correlation makes diagnosis of the acute illness rela-
tively simple because most patients have the characteristic skin lesions of chickenpox.
Chickenpox pneumonia is much more common in adults than in children.
ENVIRONMENTAL DISEASES
Silicosis and coal workers’ pneumoconiosis80,429 are the occupational diseases most
commonly associated with the pattern of diffuse fine interstitial nodules. The pre-
dicted distribution of fine nodules based on lung volume would favor a basilar pre-
dominance, but this is not the case in silicosis. The fine nodules caused by silicosis are
predominantly in the upper lobes (Fig. 17.5, A and B).214,299 Histologically, these nod-
ules are localized areas of fibrosis, and the summation of shadows probably contributes
to the nodular appearance. In many cases of silicosis, the chest radiograph shows a
fine reticular and nodular pattern, which suggests that crossing reticulations may con-
tribute to the nodular appearance. Because this a chronic, long-standing process, the
nodules may very slowly increase in size and may also calcify. Exposure to free silica
occurs in a variety of occupations including sandblasting, quarrying, and coal mining.
There is some controversy as to whether coal workers’ pneumoconiosis and silicosis
are two separate entities. Radiologic and histologic evidence indicates that the intersti-
tial reaction that results in reticulations, nodules, and conglomerate masses is a stron-
ger reaction to silica than to anthracotic pigments. In most cases, a history of exposure
is easily obtained. It is also important to compare the current chest radiograph with
old examinations to confirm the stability of the process. Patients with a history of coal
B
Fig. 17.5 A, Silicosis has caused numerous small nodules that are more conspicuous in this case
because of calcification. They have an upper lobe predominance, with the more peripheral nodules
appearing to blend in. The patient had a long history of working as a tombstone engraver. B, Coronal
computed tomography image confirms the peripheral upper lobe predominance of the nodules. Calci-
fied hilar and mediastinal lymph nodes are also consistent with silicosis. This combination could also
result from histoplasmosis.
mining are at increased risk for the development of superimposed tuberculosis or sili-
cotuberculosis. A change in the radiographic pattern or the rapid development of dif-
fuse fine, interstitial nodules, in combination with a febrile response and night sweats,
is strongly suggestive of tuberculosis rather than simple pneumoconiosis.
Other occupational exposures known to produce diffuse, fine, nodular patterns are
berylliosis,80 hypersensitivity pneumonitis,501,570 hard metal pneumoconiosis, and
Fig. 17.6 Diffuse fine nodules are a classic but uncommon appearance for lung involvement by
sarcoidosis. The expected adenopathy may regress before there is radiologic evidence of interstitial
disease. The development of diffuse fine nodular or reticular opacities is a sign that the patient is at risk
for the development of advanced pulmonary scarring.
siderosis.80,299 Asbestosis, on the other hand, is best known for producing reticular or
linear opacities, as described in Chapter 18, rather than fine nodular opacities. The
diagnosis of berylliosis is usually suggested by a history of exposure. However, the
incidence of berylliosis has become rare, primarily because the number of occupations
in which there is potential exposure to beryllium has decreased dramatically. Histori-
cally, beryllium was used as a coating for fluorescent light bulbs, and this was one of
the most common sources of exposure to the metal. It is still used in the aerospace
industry, particularly in aircraft brake linings. Confirming the diagnosis of berylliosis is
sometimes difficult because the histologic examination of the nodules reveals a granu-
lomatous reaction identical to that seen in sarcoidosis. Chemical analysis of wet tissue
is frequently required for confirmation.
Hypersensitivity pneumonitis (allergic alveolitis) is an allergy involving the alveolar
wall that results from exposure to a variety of noninvasive fungi, organic materials, and
chemicals.299,353,501,570 Hypersensitivity pneumonitis causes a number of patterns, and
fine nodular opacities are common. The HRCT patterns may be mixed, with ground-
glass, air space, fine nodules, reticular opacities, and mosaic perfusion. The observation
of fine nodules is an important feature for distinguishing hypersensitivity pneumonitis
from usual interstitial pneumonitis. The fine nodular interstitial opacities frequently
indicate a subacute or chronic phase of the illness. Histologically, the nodules cor-
respond with the presence of sarcoid-like granulomas. Sources of exposure include
moldy hay (farmer’s lung), saw dust, humidifiers, bird droppings, cork, chemicals such
as isocyanates, and use of hot tubs.
SARCOIDOSIS
Sarcoidosis is an autoimmune disease that causes an inflammatory response with granu-
lomas that spread through the bronchovascular bundles and lymphatics103 (Fig. 17.6).
Small granulomas may cause very fine nodular opacities that resemble those of miliary
tuberculosis. Sarcoidosis may be distinguished from a number of other entities consid-
ered in this differential because of their relatively mild symptoms, despite radiologic
findings that suggest a severe pathologic condition. Patients with sarcoidosis may com-
plain of very mild dyspnea and virtually no other symptoms. The combined presence
Fig. 17.7 Papillary carcinoma of the thyroid is a well-known cause of diffuse small nodular metasta-
ses. Because patients with this tumor often have a relatively long survival, the profusion may be great
and the nodules may be larger than the nodules of granulomatous infections.
of hilar adenopathy and a fine nodular pattern is an important feature to suggest sar-
coidosis, but the adenopathy often regresses as the lung disease advances. Therefore, an
old examination that demonstrates bilaterally symmetric hilar adenopathy is virtually
diagnostic of sarcoidosis. Silicosis is another entity considered in this differential of fine
nodules and hilar adenopathy, but silicosis should be confirmed with an exposure his-
tory. (Answer to question 3 is True.) Additionally, eggshell calcifications of lymph nodes
are considered a classic sign of silicosis, but they have also been observed in sarcoidosis.
Langerhans cell histiocytosis1,585 is a smoking-related disease that is best known as a
cause of upper lobe cysts, but in its earliest stages it causes interstitial nodules that also
have an upper lobe predominance. The nodules may be very small with the appear-
ance of miliary nodules but become larger as the disease progresses.
METASTATIC DISEASE
The development of a fine nodular pattern in a patient with a known distant primary
tumor, such as a thyroid tumor (Fig. 17.7),467 is strongly suggestive of disseminated meta-
static disease. These patients often have signs of severe systemic illness, including weight
loss, but careful clinical correlation is required because many patients with malignant
tumors receive chemotherapy with potent immunosuppressive agents. A febrile response
strongly suggests opportunistic infection, and prompt biopsy of the lung is advisable for
establishing the diagnosis of a treatable infectious disease. Other primary tumors that
have been observed to lead to this pattern include melanoma (Fig. 17.8, A and B), breast
cancer, and gastrointestinal tumors, including pancreatic cancer.
B
Fig. 17.8 A, Melanoma frequently metastasizes to the chest with a variety of manifestations
including numerous small nodules. These nodules often vary in size and are larger than miliary
nodules. B, Computed tomography image confirms that the nodules are well circumscribed, vary
in size, and have a basilar distribution. This is very characteristic of metastatic nodules.
Top 5 Diagnoses: Diffuse Fine Nodular Opacities

1. Miliary tuberculosis
2. Fungal infections
3. Sarcoidosis
4. Pneumoconiosis (coal workers’ pneumoconiosis, silicosis)
5. Metastases
Summary
Miliary tuberculosis is the classic example of a disease producing a fine nodular inter-
stitial pattern on radiographic examination of the chest.
The most common fungal infections that produce a fine nodular interstitial pattern are
histoplasmosis, coccidioidomycosis, and blastomycosis.
Silicosis and coal workers’ pneumoconiosis are the most common inhalational diseases
to produce the pattern. Asbestosis, in contrast, produces a reticular interstitial pattern.
Sarcoidosis and Langerhans cell histiocytosis may produce a fine nodular interstitial
pattern, although the patient may have only minimal symptoms of shortness of breath
or easy fatigability. Associated bilateral hilar adenopathy or even previous examina-
tions revealing hilar adenopathy are strongly suggestive of sarcoidosis.
Patients who are immunosuppressed are susceptible to infection by less common or-
ganisms (e.g., Nocardia, Cryptococcus, and Aspergillus), but we must not minimize the
frequency of infection by common organisms in these patients (e.g., viral pneumonia,
tuberculosis, coccidioidomycosis, histoplasmosis, and blastomycosis).
ANSWER GUIDE
Legend for introductory figures
Fig. 17.1 Diffuse fine nodular opacities are the classic radiologic appearance of miliary
tuberculosis. This patient was treated with steroids for rheumatoid arthritis and within
1 month developed the diffuse nodules. Transbronchial biopsy confirmed the diagnosis.
Fig. 17.2 Histoplasmosis is the most common cause of disseminated calcified nodules.
Chickenpox pneumonia may also heal and leave residual nodules that may calcify.
ANSWERS
1.
a 2.
e 3.
True 4. False

Chest Radio 17 Diffuse Fine Nodular Opacities

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17 DIFFUSE FINE NODULAR OPACITIES

Mark the following questions True or False:

4. _ _____ Bronchoscopy with biopsy is contraindicated in the evaluation of patients in

Chart 17.1 DIFFUSE FINE NODULAR OPACITIES

followed by larger, multifocal, ill-defined opacities or even diffuse coalescent opacities

Top 5 Diagnoses: Diffuse Fine Nodular Opacities

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Chest Radio 17 Diffuse Fine Nodular Opacities

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17 DIFFUSE FINE NODULAR OPACITIES

Mark the following questions True or False:

4. _ _____ Bronchoscopy with biopsy is contraindicated in the evaluation of patients in

Chart 17.1 DIFFUSE FINE NODULAR OPACITIES

followed by larger, multifocal, ill-defined opacities or even diffuse coalescent opacities

Top 5 Diagnoses: Diffuse Fine Nodular Opacities

You might also like

4. _ _____ Bronchoscopy with biopsy is contraindicated in the evaluation of patients in

Chart 17.1 DIFFUSE FINE NODULAR OPACITIES