Diffuse Lung Diseases Associated with Calcification

W. Richard Webb

A wide variety of lung diseases may be associated with some degree of lung calcification, most notably granulomatous diseases such as sarcoidosis or tuberculosis (Table 21-1).

Several diffuse lung diseases are associated with extensive lung calcification as a common finding or as a primary manifestation of the disease. These are discussed in this chapter.

DIFFUSE PARENCHYMAL AMYLOIDOSIS

The term amyloidosis refers to a group of conditions characterized by extracellular deposition of abnormal fibrillar protein. Amyloidosis may be classified according to its etiology, the proteins involved, or its primary manifestation (Table 21-2). The first two of these categories overlap, are somewhat confusing, and are reviewed briefly. Classification according to its primary manifestation is most appropriate to the radiologic assessment of amyloidosis and is easiest to remember.

Classification by Etiology

An etiologic classification of amyloidosis includes (1) primary amyloidosis (i.e., associated with a plasma cell disorder or idiopathic); (2) secondary amyloidosis (i.e., associated with chronic inflammatory disorders or neoplasms such as Hodgkin’s disease); (3) heredofamilial amyloidosis (i.e., having a genetic basis); and (4) senile amyloidosis, which usually occurs in patients over the age of 70.

It may be subdivided into systemic forms (i.e., diffuse involvement of multiple organs) or localized forms (i.e., focal involvement largely limited to one organ).

Classification by Specific Proteins

When amyloidosis is classified according to the specific abnormal protein involved, the most important types producing lung disease are amyloid L and amyloid A.

Amyloid L (AL, or light chain amyloidosis) is the most common form of systemic amyloidosis. It may be either idiopathic or associated with plasma cell disorders (about 90% of cases). The lung is involved in 70% to 90% of patients with AL amyloidosis. Cardiomyopathy almost always is present if the lung is involved. Prognosis generally is poor. AL amyloidosis also may result in localized lung involvement. AL typically occurs in patients in their 50s or 60s.

Amyloid A (AA) occurs as secondary amyloidosis in patients with chronic inflammatory diseases (e.g., collagen vascular disease, infections, inflammatory bowel disease, and familial Mediterranean fever) and some neoplasms such as Hodgkin’s disease. The lung is commonly involved to some degree, but deposits often are small or clinically insignificant. The prognosis is better than that for AL.

Among patients who have pulmonary involvement by amyloid, about 65% have primary systemic amyloidosis (systemic AL), 30% have localized amyloidosis (localized AL), and 5% have secondary amyloidosis (AA).

Classification by Manifestation

From a radiographic standpoint, it is most useful to classify amyloidosis on the basis of the abnormalities it produces. In general, pulmonary amyloidosis is classified
into three types: (1) diffuse or alveolar septal amyloidosis, (2) localized nodular amyloidosis, and (3) tracheobronchial amyloidosis.

TABLE 21.1 Diffuse or Multifocal Lung Calcification

Infectious diseases
	Tuberculosis
	Histoplasmosis
	Healed varicella pneumonia
	Parasitic infections
Sarcoidosis
Silicosis and coal-worker’s, pneumoconiosis
Calcified metastases
	Osteogenic and chondrosarcoma
	Mucinous adenocarcinoma
	Thyroid carcinoma
Pulmonary ossification with mitral stenosis
Lung fibrosis with dystrophic calcification
Amyloidosis
Alveolar microlithiasis
Metastatic calcification

TABLE 21.2 Classification of Amyloidosis

By etiology
Primary amyloidosis—plasma cell disorder or unassociated with underlying disease
Secondary amyloidosis—associated with chronic inflammatory disorders or neoplasm
Heredofamilial amyloidosis
Senile amyloidosis—usually in patients over 70
Systemic (diffuse involvement of multiple organs)
Localized (focal involvement largely limited to one organ)
By specific proteins
Amyloid L (AL; light-chain amyloidosis)
	Most common
	Usually primary amyloidosis
	Lung involved in 70%-90%, localized or diffuse
	Cardiac involvement
	Poor prognosis
Amyloid A
	Secondary amyloidosis
	Lung involved to a minor degree
	Better prognosis
By manifestation
Diffuse (alveolar septal) amyloidosis
	Usually primary systemic and AL
	Dyspnea due to lung or heart disease
	Small nodules or reticular opacities
	Consolidation
	Lymph node enlargement
	Calcification common
Localized nodular amyloidosis
	Usually primary localized and AL
	Usually asymptomatic
	Lung nodules, often calcified
	Nodules grow slowly
Localized tracheobronchial amyloidosis
	Usually primary localized and AL
	Tracheal and bronchial narrowing or masses
	Calcification common

Diffuse (Alveolar Septal) Amyloidosis

Symptoms of respiratory insufficiency are common with diffuse or alveolar septal amyloidosis, and may be related to diffuse lung disease or associated cardiac involvement. This form of amyloidosis is most often related to primary systemic amyloidosis (systemic AL). Diffuse lung involvement is much less common and may be incidental with AA amyloidosis or senile amyloidosis. Occasionally, diffuse alveolar septal amyloidosis reflects localized rather than systemic disease.

The lung may be diffusely involved in the absence of a radiographic abnormality. If radiographs are abnormal, a reticular or reticulonodular pattern typically is seen, usually bilateral and diffuse or with a basal and subpleural predominance (Figs. 21-1 and 21-2A). Focal or patchy areas of consolidation also may be seen. The abnormal areas can calcify or, rarely, show frank ossification. Less often, a small nodular pattern mimicking sarcoidosis or miliary tuberculosis may be seen.

Hilar or mediastinal lymph node enlargement may be seen in patients with AL, either as an isolated finding or in association with interstitial disease. Cardiac infiltration with heart failure may result in pulmonary edema or pleural effusion.

On HRCT, the most common pulmonary manifestations of diffuse parenchymal amyloidosis consist of multiple small nodules, usually ranging from 2 to 4 mm in diameter (see Fig. 21-2B and C), interlobular septal thickening, fine reticular opacities, focal consolidation, foci of calcification within nodules or areas of consolidation (Fig. 21-3), and traction bronchiectasis. A subpleural and basal predominance may be seen.

Progression of the diffuse parenchymal disease typically occurs with time, with an increase in the reticular opacities, septal thickening, the size and number of nodules, the extent of consolidation, and the size and number of calci-fications.

As on chest radiographs, other findings seen on CT include lymphadenopathy, lymph node calcification (Fig. 21-4), and pleural effusion. Lymph node enlargement occurs in up to 75% of cases.

FIG. 21.1. Diffuse alveolar septal amyloidosis. A diffuse reticulonodular pattern is visible, with the abnormality predominating at the lung bases. Lung and lymph node calcification is present, and the heart is enlarged.

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