Septal thickening: HRCT findings and differential diagnosis

Septal Thickening: HRCT Findings and Differential Diagnosis J. Andreu,a A. Hidalgo,a E. Pallisa,a J. Majó,b M. Martinez-Rodriguez,a and J. Cáceres,a

Thickening of the interlobular septa is a common and easily recognized high-resolution computed tomography feature of many diffuse lung diseases. In some cases, it is the predominant radiological finding. This article reviews the spectrum of entities that commonly present with thickening of the interlobular septa as the main radiological feature and establishes a practical approach for the differential diagnosis.

The secondary pulmonary lobule is the smallest anatomic unit that can be properly studied by highresolution computed tomography (HRCT). It has a polyhedral structure, is composed of several groups of pulmonary acini ranging in size from 1 to 2.5 cm, and is surrounded by sheets of connective tissue containing pulmonary veins and lymphatic vessels. This connective tissue bounds the lobules and forms the interlobular septa, which are the most visible part of the peripheral lung interstitium. The normal distribution and morphology of the interlobular septa is not homogeneous. They are more numerous and thicker in the anterior and lateral regions of the upper and middle lobes, and in the anterior, diaphragmatic, and mediastinal areas of the lower lobes.1 On HRCT, normal interlobular septa are not generally visible, but several pathologic conditions present with septal thickening, which is easily recognizable. Nevertheless, the group of entities with this feature is quite heterogeneous and radiological studies are needed to help establish the differential diagnosis. To From the Departments of aRadiology and bPathology, HGU Vall d’Hebron, Autonomous University of Barcelona, Barcelona, Spain. Reprint requests: J. Andreu, MD, Department of Radiology, HGU Vall d’Hebron, Paseo Vall d’Hebron 119, Barcelona 08035, Spain. Curr Probl Diagn Radiol 2004;33:226-37. © 2004 Elsevier Inc. All rights reserved. 0363-0188/2004/$30.00 ⫹ 0 doi:10.1067/j.cpradiol.2004.06.001

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simplify the radiological approach to processes with septal thickening, we have established the four following main groups based on the appearance of the septa and the cause of the disease: 1. Edematous processes, whose main radiologic finding is smooth septal thickening due to filling by fluid. 2. Infiltrative diseases, such as tumors or tumor-like entities, which present with nodular septal thickening. 3. Fibrotic conditions, including interstitial fibrosis of any cause, which present with irregular septal thickening and marked distortion of the lung. 4. Miscellaneous processes that manifest septal thickening or simulate this feature.

Edematous Thickening In edematous thickening, the septa are filled with fluid and appear as smooth, regular, linear structures on HRCT. Depending on the type of fluid, the four following groups of entities can be defined: edema, hemorrhage, infection, and lymphatic lesions. Most of these processes are clinically acute, but subacute and chronic presentations are sometimes observed. The clinical setting and the associated radiological features will help in the etiological diagnosis.

Edema The most common cause of edematous thickening is congestive heart disease, but there are other noncardiogenic causes, such as renal failure. In heart disease, septal thickening is diffuse and bilateral and is often associated with alveolar opacities (Fig 1). Enlargement of the heart, bilateral pleural effusion, and clinical presentation facilitate the diagnosis (Fig 2).2 In chronic conditions, such as long-term mitral steno-

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FIG 1. Cardiac failure presenting with smooth septal thickening.

FIG 3. Pulmonary hemorrhage. Crazy-paving pattern consisting of areas of ground-glass attenuation with septal thickening.

FIG 2. Heart failure. Cardiac enlargement and bilateral pleural effusion.

sis, most of the septal thickening corresponds to fibrosis rather than to edema. In atypical cases of edema, the diagnosis may be difficult. Asymmetrical edema is unusual and is mainly related to underlying lung abnormalities such as emphysema or to re-expansion of a collapsed lung.3

Hemorrhage Pulmonary hemorrhage occurs with ground-glass areas and air-space consolidation as well as septal thickening.4 The thickening appears days after the onset of the condition and is often associated with ground-glass opacities, producing the so-called “crazy-paving” pattern (Fig 3). Septal thickening as the only radiologic feature of pulmonary hemorrhage is rarely observed.

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FIG 4. Lung transplantation. Edematous pattern is associated with CMV infection.

Infection Septal thickening is a common finding in acute pneumonia of any etiology and is particularly frequent

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FIG 6. Lymphangioleiomyomatosis. Septal thickening (arrows) secondary to lymphatic edema.

FIG 5. (A and B) Lymphangiomatosis. Diffuse, smooth septal thickening and several small areas of ground-glass opacities (arrows).

in viral pneumonia. It is rarely the main radiologic feature and is usually associated with air-space consolidation, ground-glass areas, or centrilobular branching structures (Fig 4).5

Primary Lymphatic Lesions This section includes rare diffuse lung entities, such as lymphangioleiomyomatosis, lymphangiomatosis, and lymphangiectasia, which present with dilation or proliferation of the lymphatic channels. In lymphangiomatosis,6,7 there are diffusely increased pulmonary lymphatic spaces and lymph accumulation. Smooth thickening of the interlobular septa and the bronchovascular bundles are the main radiological features. Patchy areas of ground glass are often present and correspond to associated areas of hemorrhage or edema (Fig 5).7 Lymphangioleiomyomatosis is characterized by the presence of lung cysts. Reticular opacities are related to interstitial edema secondary to obstruction of the lymphatic vessels, an uncommon finding in this illness (Fig 6).8

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FIG 7. Lymphangitic metastasis. Nodular septal thickening (arrows).

Infiltrative Thickening The most characteristic feature in the infiltrative group is nodular septal thickening, caused by tumor growth within the septal space. In some cases, edema secondary to hilar lymphatic blockage is also present. Many of the processes in this group, such as lymphangitic metastasis, lymphoma, or amyloidosis, commonly have a subacute clinical presentation.

Lymphangitic Metastasis Lymphangitic metastasis is a typical form of lung metastasis presenting as diffuse thickening of the

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FIG 8. (A and B) Lymphangitic metastases. Typical polygonal structure with central nodular opacities.

FIG 9. Lymphangitic metastasis. Large cavitated nodule (arrow).

interstitium.9,10 Any primary tumors may present with this type of lung metastasis, but it is more commonly seen in adenocarcinomas from the breast, lung, gastrointestinal tract, or prostate.11,12 The pathogenesis of lymphangitic spread is not clear.13 It is believed that hematogenous embolism of tumors to pulmonary arterioles and capillaries (as in cases of miliary tuberculosis) first occurs, and then lymphatic dissemination is produced. In other cases, particularly in primary lung neoplasms, there is direct extension from a hilar or mediastinal tumor; the

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edematous component predominates over the infiltrative component in this situation. Lymphangitic metastasis is rarely asymptomatic. Usually there is progressive dyspnea, which can be severe, and a subacute presentation. Dyspnea may be the first symptom of the tumoral process. A clinical presentation mimicking asthma has also been observed. In approximately 25% of the cases, the chest radiograph is normal.14 Reticular, linear patterns are often seen, and less commonly, reticulonodular patterns. HRCT shows thickening of the septa and peribronchovascular interstitium without significant distortion of the lung parenchyma. The morphology of the septa is irregular or nodular and has a beaded appearance (Fig 7).15,16 This beaded appearance is typical of lymphangitic metastasis and is not present in other entities involving septal thickening, such as edema or fibrosis. The linear opacities may form polygonal structures with central nodular opacities representing prominent bronchovascular bundles (Fig 8). Larger nodules that may be cavitated are often seen (Fig 9). Common associated features are pleural effusion and hilar lymph node enlargement (Fig 10). Lymphangitic metastasis is often an asymmetric process, and is seen in half the cases (Fig 11).16 Unilateral involvement is also commonly seen in the early stages of disease and is most frequently associated with lung and breast neoplasms (Fig 12). Segmental or lobar focal involvement is also reported.

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FIG 11. Lymphangitic metastasis. Focal lung involvement.

FIG 10. (A and B) Lymphangitic metastases. Pleural effusion and hilar mass are common associated features.

Peripheral predominance is most common, although central predominance is also seen. Predominantly, central involvement tends to cause less respiratory dysfunction.17 Although lymphangitic metastasis is associated with an unfavorable prognosis, it can resolve with chemotherapy (Fig 13).18,19

Fibrotic Thickening Several entities present with interstitial fibrosis. Various disorders of unknown etiology are included in this group, as well as processes secondary to specific causes such as asbestos-related disease, collagen-vascular diseases, radiation exposure, and drug toxicity.

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FIG 12. Lymphangitic metastasis. Unilateral involvement; note the severe bronchovascular thickening.

The most characteristic HRCT finding in these conditions is a honeycomb pattern due to the presence of numerous small cysts, particularly in the peripheral lung. Marked interlobular septal thickening may be associated with the honeycombing and is often observed in the initial phases. The septa present as irregular linear opacities that are prominent in the subpleural regions. Additionally, thickening of the intralobular interstitium produces a fine reticular pattern associated with the septal thickening. These abnormalities result in

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FIG 13. (A and B) Lymphangitic metastasis. (A) Severe lymphatic pattern. (B) Resolution after intensive chemotherapy.

marked parenchymal distortion, which is also a characteristic feature in this group of diseases.

Idiopathic Pulmonary Fibrosis The prognosis of idiopathic pulmonary fibrosis is poor because there is little, if any, response to treatment. The fibrosis is not uniform; areas of normal lung are interspersed among areas of honeycomb destruction (Fig 14). Other types of interstitial pneumonia having different radiological presentations may have a better prognosis.20,21

Collagen-Vascular Disease Collagen-vascular disease is usually associated with a reticular or linear pattern, and ground-glass opacities are common. The characteristic clinical features and the relatively unusual presence of honeycombing are clues to the proper diagnosis (Fig 15).

Radiation-Induced Disease In the acute phase, the main finding of radiation lung disease is pneumonitis. In the chronic stage, fibrous changes are observed, including atelectasis and lung distortion. Prominent interlobular pleural septa are seen in rare cases (Fig 16). The history of irradiation and the limitation of lung involvement to the irradiated area help to establish the diagnosis.

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Asbestosis Lung abnormalities secondary to asbestos exposure are predominantly located in subpleural areas (Fig 17). Some cases are indistinguishable from idiopathic pulmonary fibrosis but mild subpleural lung disease manifesting as linear or nodular opacities associated with pleural plaques usually makes the diagnosis possible (Fig 18). Pleural plaques, which may be calcified, are the most common asbestos-related abnormality and constitute the radiological hallmark of asbestos disease (Fig 19).22

Miscellaneous Conditions This section includes rare processes associated with pulmonary artery obstruction. Chronic obstruction of the main pulmonary vessels produces a fine reticular lung pattern that may be due to associated obstruction of lymphatic drainage, which causes septal thickening, or to the presence of systemic-pulmonary anastomoses that simulate septal thickening. This feature is observed in congenital or acquired entities and is usually unilateral.23

Absence of Proximal Right Pulmonary Artery Absence of the proximal right pulmonary artery is a rare, congenital, usually isolated thoracic vascular

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FIG 15. (A and B) Scleroderma. Subpleural involvement with some marked interlobular septa.

Radiological features include a unilateral small lung, without visualization of the pulmonary artery or its main branches. Marked intercostal and bronchial collateral circulation is observed. Shunts in the subpleural space mimic septal thickening (Fig 18).

Takayasu Arteritis FIG 14. (A-C) Idiopathic pulmonary fibrosis with septal thickening (arrows) and honeycombing.

malformation.24 Cardiac abnormalities are often associated with this condition.

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Pulmonary artery involvement is observed in around half of the patients with Takayasu arteritis. In infrequent, severe cases, chronic obstruction of the pulmonary artery may produce several pulmonary shunts (Fig 20).25,26

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FIG 16. (A and B) Radiation pneumonitis in chronic stage. Interlobular septal thickening.

Fibrosing Mediastinitis Any type of slow-growing mediastinal mass with secondary pulmonary artery obstruction can produce systemic-pulmonary anastomoses. We have seen this in cases of fibrosing mediastinitis (Fig 21). This rare process, which is related to an abnormal response to granulomatous infections, produces an infiltrative mediastinal mass, more commonly on the right, that can affect any vascular structure of the mediastinum.27

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FIG 17. (A and B) Asbestosis. (A) Initial fibrosis. (B) Advanced process with prominent septa.

Conclusion HRCT is a useful tool for the study of patients with septal thickening as a major feature. The type of thickening (smooth, nodular, or irregular), the presence of distortion of the lung, and the clinical features point to the proper diagnosis in most cases.

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FIG 18. (A-C) Absence of proximal pulmonary artery. (A and B) Small right hemithorax with septal thickening. (C) Absence of pulmonary artery. Note mild widening of the pleural space.

Acknowledgment We thank Celine Cavallo for English-language assistance.

FIG 19. Asbestosis. Multiple pleural plaques, some of them calcified, are noted as a biomarker of exposure.

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FIG 20. (A-D) Takayasu arteritis. (A) Prominent right septa. (B,C) Pulmonary artery obstruction. (D) Marked subpleural vessels.

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FIG 21. (A-C) Fibrosing mediastinitis. (A,B) Fine unilateral reticular pattern. (C) Soft tissue mass producing pulmonary artery obstruction.

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