Presentation and Diagnosis of Interstitial Lung Diseases

Abstract

Diffuse interstitial lung disease is a heterogeneous group of lung pathologies with similar clinical presentations. Radiologists and pathologists attempted to identify precise diagnostic criteria. Often, the pattern and distribution of the disease allow to narrow down the possible diagnoses, but the correlation with the clinical presentation is essential.

Diffuse interstitial lung disease is a heterogeneous group of lung pathologies with similar clinical presentations. Radiologists and pathologists attempted to identify precise diagnostic criteria. Often, the pattern and distribution of the disease allow to narrow down the possible diagnoses, but the correlation with the clinical presentation is essential.

The main radiological patterns are:

• Nodular

• Septal

• Cystic

• Alveolar (ground-glass)

• Reticular

• Honeycombing

To recognize the radiological pattern of the disease, it is necessary to search and study on HRCT images the secondary pulmonary lobule (SPL) that is the smallest structural unit in the lung. It is a roughly polyhedral structure, 1–2 cm in size, lined by connective tissue septa; the lobules in the peripheral regions of the lung are larger and more regular in shape, becoming smaller and more irregular in the central portions. Each SPL is constituted by 3–15 acini and 30–50 alveoli and is fed by a small lobular bronchiole and a pulmonary artery branch. These structures run in parallel in the central portion of the lobule and are therefore described as centrilobular. In the peripheral region, the venous and lymphatic vessels are contained in the interlobular interstitium.

The SPL is composed by three main elements:

• The interlobular septa: normally about 0.1 mm thick and therefore not visible on HRCT except in the peripheral region where they are slightly thicker and can barely be identified. The venous branches running within them have a caliber of about 0.5 mm and can, therefore, be visualized. Diseases affecting the venous or lymphatic systems of the lung will affect this region, e.g., “perilobular” patterns.

• The centrilobular structures: consist of the intralobular arterial and bronchial branches. In normal conditions, it is possible to identify the lobular artery (1 mm), the terminal artery (0.7 mm), and the acinar artery (0.5 mm). The bronchial branches contain air and cannot be visualized as their wall thickness is inferior to the lower limit of resolution on HRCT (0.15 mm). When the bronchiolar lumens become plugged with dense materials such as fluids, blood, or pus, the tracings of the intralobular branches become visible on HRCT as branched structures terminating in small nodules (tree-in-bud appearance).

• The lobular parenchyma and acini: not visible on HRCT under normal conditions. They include the functional units of the lung, i.e., the alveoli and the capillary bed with their supportive structures of connective tissue (intralobular interstitium). In some pathologies, e.g., inflammatory diseases, the involvement of the acinus appears as a small intralobular nodular opacity, about 0.6–1 mm in size.

Nodular Pattern

The nodular pattern is characterized by nodules less than 1 cm in size with variable characteristics and distribution, based on which it can subdivided into:

• Nodules in a random pattern (Fig. 9.1)

• Nodules in a miliary pattern (Figs. 9.1 and 9.2)

• Nodules in a centrilobular (or bronchovascular) pattern (Fig. 9.3)

• Nodules in a lymphatic or perilymphatic pattern (Fig. 9.4)

Fig. 9.1

Nodules in a random pattern

Fig. 9.2

Patient with miliary dissemination of tuberculosis

Fig. 9.3

Nodules in a centrilobular pattern

Fig. 9.4

Nodules in a lymphatic or perilymphatic pattern

Nodules in a Random Pattern

They are usually secondary to pathologies with hematogenous dissemination (Table 9.1). Thus, they are:

• Diffuse (and never focal, as can occur in the bronchovascular pattern)

• More numerous in the periphery (within 2–3 cm from the pleura) and at the bases (where there is more blood flow)

• Possibly associated to a feeding vessel, that is, an arterial vessel entering the nodule (Fig. 9.1, in the center)

Table 9.1 Differential diagnosis of nodules in a random pattern

If they are few in number, it may be difficult to distinguish this pattern from a centrilobular or perilymphatic one.

Nodules in a Miliary Pattern

They are secondary to pathologies with hematogenous dissemination (Tables 9.2 and 9.3) and have the following characteristics:

• Small nodules (<5 mm), too many to be counted (Fig. 9.1, lower part; Fig. 9.2);

• Random distribution within the SPL.

Table 9.2 Differential diagnosis of nodules in a miliary pattern

Table 9.3 Differential diagnosis between mycobacterial miliary nodules and metastases

CXR may be negative due to their small size.

Dense or calcific nodules in a miliary pattern can be secondary to healed histoplasmosis, healed chickenpox, thyroid metastases after radioactive Iodine-131 treatment, talcosis, and pulmonary alveolar microlithiasis.

Nodules in a Centrilobular Pattern

These nodules are located in the bronchovascular core of the SPL and are a typical manifestation of bronchiolocentric or bronchiolar interstitial lung diseases (Table 9.4). They are:

• Located at least 5–10 mm from the pleural surface or the interlobar fissures or the SPL margins

• Generally of ground-glass density

• Associated to other signs of bronchiolar obstruction:

  • Tree-in-bud opacities: the bronchioles are dilated and plugged by dense contents (mucus, pus, or fluid) and peribronchial inflammation is present

  • Mosaic pattern: due to hyperinflation of some SPLs

• Common in bronchiectasis of any cause

Table 9.4 Differential diagnosis of nodules in a centrilobular pattern

Nodules in a Lymphatic or Perilymphatic Pattern

These are nodules located around the lymphatic vessels and the perilymphatic channels (Figs. 9.4 and 9.5; Table 9.5). Their characteristics are as follows:

• Well-defined nodules (2–5 mm)

• Axial distribution: in the peribronchovascular interstitium, from the hilum to the periphery

• Peripheral distribution: in the subpleural interstitium, in the interstitium of fissures and SPL contour

• Associated to involvement of mediastinal lymph nodes

Fig. 9.5

Nodules in a perilymphatic pattern in a patient with sarcoidosis

Table 9.5 Differential diagnosis of nodules in a perilymphatic pattern

Some diseases can start as a bronchovascular pattern (through inhalation) and then progress to a lymphatic pattern (through dissemination).

Differential Diagnosis of Nodular Patterns

The distinction of the nodular patterns depends mostly on the location, pattern, and appearance of the nodules (Table 9.6). The presence of accessory signs of airways obstruction, such as a mosaic pattern or tree-in-bud opacities, can help to distinguish the centrilobular pattern from the others, in which they rarely occur.

Table 9.6 Differences between nodular patterns

• Tree-in-bud opacities (TIB): They appear as quite defined centrilobular nodules (2–4 mm) from which linear opacities spread out in three or four V-shaped or Y-shaped branches (Fig. 9.6). They correlate to bronchiolar pathologies and are caused by the dilation of the bronchiolar lumen, filled with mucus, pus, or fluid, and to the thickening of their walls. Rarely, they can be secondary to pathologies with hematogenous dissemination such as metastatic tumors or intravenous drug abuse, which can cause arteriolar dilation (Table 9.7).

• Mosaic pattern: There are areas of attenuation corresponding to the SPL (Fig. 9.7; Tables 9.8 and 9.9). It can be caused by:

  • Obstruction of the small airways: emphysematous areas due to air-trapping

  • Vascular occlusive diseases: less vascularized areas. Usually, bronchoconstriction with air-trapping is also present in these regions as the lung attempts to maintain the ventilation-perfusion ratio within normal values

  • Patchy lung diseases: ground-glass opacification of only some SPL

  • Mixed: interstitial and small-airways disease

  It can be observed in 60% of normal subjects during expiration (maximum 1 lobule per CT section, mainly in the superior and ventral lobes).

  It can be difficult to recognize if almost all lobules are hyperextended.

Fig. 9.6

Tree-in-bud opacities in a patient with tuberculosis: (a) axial view, (b) coronal view

Table 9.7 Differential diagnosis of tree-in-bud opacities (TIB)

Fig. 9.7

Mosaic pattern

Table 9.8 Differences between mosaic patterns of different etiologies

Table 9.9 Differential diagnosis of mosaic pattern

Septal Pattern

It represents the interlobular septal thickening of the SPL and is seen as short lines in the periphery of the lung that arrive to the pleura. They can have different morphology: smooth, nodular, irregular.

The most common diagnoses are (Tables 9.10 and 9.11):

• Pulmonary edema: smooth (Figs. 9.8a and 9.9)

• Pulmonary fibrosis: irregular

• Lymphangitic carcinomatosis: smooth or nodular (Fig. 9.8b). It can be associated with the following:

  • Prevalently septal pattern with nodular and irregular thickening

  • Often entire lobes or the contralateral lung are spared

  • Hilar lymphadenopathy

Table 9.10 Differential diagnosis of septal pattern (acute forms)

Table 9.11 Differential diagnosis of septal pattern (subacute and chronic forms)

Fig. 9.8

Septal pattern: (a) Smooth septal thickening, (b) Nodular septal thickening, (c) Ground-glass with superimposed septal thickening, also called “crazy paving” pattern

Fig. 9.9

Septal pattern with smooth septal thickening in a patient with non-cardiogenic pulmonary edema secondary to CHT

Fig. 9.10

Cystic pattern: (a) Langerhans cell granulomatosis. Characteristically dysmorphic thin-walled cysts. (b) Lymphangioleiomyomatosis

The septal pattern can be associated with ground-glass opacities, leading to the so-called crazy paving pattern (Fig. 9.8c). This was initially described in pulmonary alveolar proteinosis, where the ground-glass appearance is due to the partial alveolar filling with proteinaceous material, and the septal pattern is due to the thickening of the SPL’s septa or the accumulation of material at the periphery of the air spaces.

Cystic Pattern

It is characterized by air-filled or fluid-filled spaces with more or less defined walls. Superior lobes are more involved because the apical regions of the lung are subjected to greater gravity-induced stretching. All diseases causing a cystic pattern increase the risk of pneumothorax (Table 9.12).

Table 9.12 Differential diagnosis of cystic pattern

Initially, pulmonary function tests show a restrictive pattern with reduction of lung diffusion for CO; later, they present an obstructive pattern.

Alveolar Pattern: Ground-Glass Opacities

The alveolar patterns are ground-glass opacity and parenchymal consolidation.

The ground-glass opacities are characterized by an increased opacity of the lung parenchyma that does not obscure the underlying structures (Fig. 9.11). In the pulmonary consolidation, the bronchovascular structures are obscured.

Fig. 9.11

Alveolar pattern. Ground-glass opacity in a patient with NSIP

Fig. 9.12

Reticular pattern in a patient with NSIP

Ground-glass opacities represent an acute process or an acute flare of a chronic disease (Table 9.13). The radiological presentation is due to:

• Partial filling of air spaces (edema, hemorrhage, pus)

• Interstitial thickening secondary to edema, inflammation, or fibrosis, usually associated to a reticular pattern or traction bronchiectasis

• Tumor growth preserving the parenchymal structures

Table 9.13 Differential diagnosis of alveolar pattern (ground-glass opacity)

Reticular Pattern

The reticular pattern is characterized by small and numerous intralobular linear opacities (Table 9.14). As the disease progresses, interlobular septal thickening and traction bronchiectasis are observed.

Table 9.14 Differential diagnosis of reticular pattern

Honeycombing

It represents a fibrotic and severely damaged lung, characteristic of end-stage lung disease. It presents with multiple well-defined small cysts, from 3–10 mm in size up to 2.5 cm, uniform in size and clustered together. They are associated to traction bronchiectasis (Fig. 9.13).

Fig. 9.13

Honeycombing in a patient with IPF

The diagnosis is challenging as it usually represents an advanced stage of a lung disease and the biopsy is often non-conclusive (Table 9.15).

Table 9.15 Differential diagnosis of honeycombing