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Diffuse Fine Nodular Opacities
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.
- a.
- 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.
- a.
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.
Discussion
Detection of very small nodules is a serious challenge for the radiologist. Nodules measuring 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 nodular 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 differential. If the pattern includes small, fluffy, or ill-defined opacities, then alveolar edema, exudate, or hemorrhage should be considered. The presence of ill-defined borders 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 interstitial and are thus associated with one of the entities listed in Chart 17.1 .
Chart 17.1
Diffuse Fine Nodular Opacities
- I.
Infections
- II.
Environmental diseases
- III.
- III.
- VIII.
Metastatic tumor 175
- A.
Thyroid carcinoma
- B.
Melanoma 76
- C.
Other adenocarcinomas (e.g., gastrointestinal tumors)
- A.
- IX.
Other
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 members 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 radiologist 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 steroids 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 ). Miliary tuberculosis has a high mortality rate, which requires prompt diagnosis and treatment (answer to question 1 is a ).
Any of the fungal infections listed in Chart 17.1 may mimic the radiologic appearance of miliary tuberculosis, but this pattern is most commonly the result of histoplasmosis, 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, influenza-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, similar 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 pulmonary 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 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 relatively simple because most patients have the characteristic skin lesions of chickenpox. Chickenpox pneumonia is much more common in adults than in children.
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