Physiopathology

 Lymphangitic carcinomatosis represents the metastatic spread of the tumour thorough the pulmonary lymphatics. This may happen through a direct lymphatic dissemination from the mediastinal and hilar lymphatic nodes or, more frequently, from primarily hematogenous dissemination followed by lymphatic invasion. This process results in lymphatic obstruction, interstitial oedema, and subsequent structural changes, generating progressive respiratory symptoms.(4)

Imaging Findings

The radiographic manifestations of lymphangitic carcinomatosis can be categorized based on involvement of the peripheric interlobular septa and/or central lymphatic systems (Figure 1). The disease may present with diffuse involvement of both compartments or predominantly affect one. The distribution of these changes is typically variable, often appearing asymmetric and patchy.(5) While it is usually bilateral, unilateral involvement can occur, particularly in cases associated with primary lung or breast cancers.

Conventional chest radiography can provide initial insights into the presence of LC, although its sensitivity is limited. The hallmark of LC on chest radiographs is a reticulonodular pattern (Figure 2), indicative of interlobular septal thickening. (6) These septa become prominent due to the infiltration of malignant cells and resultant oedema. Radiographically, this manifests as fine, linear, or nodular opacities predominantly in the peripheral regions of the lungs. These findings, however, are often subtle and non-specific, necessitating further imaging for definitive diagnosis.(2,5)

High-resolution computed tomography (HRCT) is the gold standard for imaging in LC, being an indispensable diagnostic tool in this process, offering superior sensitivity and specificity compared to chest radiography. HRCT provides highly detailed images of the lung parenchyma and interstitial structures, allowing for the precise identification of subtle abnormalities. Thus, HRCT enables the identification of characteristic findings associated with LC. These findings are critical for distinguishing LC from other interstitial lung diseases, which may present with overlapping but distinct imaging patterns.(3)

Interlobular septal thickening is the most consistent (Figure 3). The thickening is often nodular and irregular, though it can also present as smooth. The irregularity is due to the uneven distribution of tumour cells within the lymphatics. The thickened interlobular septa may outline secondary pulmonary lobules, forming polygonal shapes. 

The lymphatic involvement around the bronchovascular bundles leads to thickening and increased visibility of the their sheaths (Figure 4). This finding may predominate over interlobular septal thickening in certain cases. The association between thickened interlobular septa creating polygonal shapes, akin to a box, and the prominent centrilobular bronchovascular bundle representing the central point within these polygonal structures, establish the “dot-in-box” sign (Figure 5).

Small nodules can be observed along the pleura as well as within the fissures that separate the different lobes of the lungs. These nodules, known as subpleural nodules (Figure 6), arise from the dissemination of malignant cells via the subpleural lymphatic vessels.

Furthermore, areas of ground-glass opacity may also be identified on imaging studies. These areas are typically caused by interstitial oedema and inflammation, which occur secondary to the obstruction of lymphatic drainage by malignant cells. The resulting fluid accumulation and inflammatory response within the interstitium and lymphatic vessels lead to these characteristic imaging findings. 

Pleural effusions are frequently encountered as an additional finding in patients diagnosed with LC (Figure 6). Despite their lack of specificity, their presence in conjunction with other characteristic imaging features can be indicative of LC. Additionally, the involvement of lymph nodes in the mediastinum—and the hilum is commonly observed in LC. Lymphadenopathies are present in approximately 30-50% of LC cases and, when correlated with other imaging findings, they reinforce the suspicion of LC and aids in differentiating it from other interstitial lung diseases.(1,2,7)

Differential Diagnosis

Accurate differential diagnosis is crucial to avoid misdiagnosis and ensure appropriate treatment. Pulmonary oedema results from fluid accumulation in the lung interstitium and alveoli, often secondary to heart failure. On imaging, it typically presents with smooth bilateral and symmetrical septal thickening and ground-glass opacities. Unlike LC, it has a gravitational distribution, predominantly affecting the lower lung zones. The presence of cardiomegaly and pleural effusions further supports the diagnosis of pulmonary oedema (Figure 7).(8)

Sarcoidosis is a systemic granulomatous disease that frequently involves the lungs, characterized by noncaseous granulomas (Figure 8). Imaging features include perilymphatic nodules, typically in a perihilar and upper lobe distribution, alongside mediastinal lymphadenopathy. (9)

Idiopathic Pulmonary Fibrosis (IPF) is a chronic fibrosing interstitial pneumopathy of unknown etiology, primarily affecting older adults. It presents with subpleural and basal-predominant reticulation, honeycombing and traction bronchiectasis. While both LC and IPF feature interstitial thickening, the presence of honeycombing and the absence of nodular septal thickening help differentiate IPF from LC.(10)

Primary pulmonary lymphoma and secondary involvement of the lungs by systemic lymphoma can mimic LC. Imaging features include peribronchovascular and interstitial infiltrates, which may appear similar to LC. However, lymphoma often presents with larger, more confluent masses and extensive lymphadenopathy.(11)

Certain infections, such as viral pneumonias (Figure 9), Pneumocystis jirovecii pneumonia, and mycobacterial infections, can present with interstitial patterns on imaging. These infections often show a patchier distribution and may be associated with other signs of infection, such as cavitation, consolidation, and air bronchograms, which are less typical in LC.(12,13)

Accurately diagnosing LC necessitates a comprehensive understanding of a broad spectrum of interstitial lung diseases and their distinctive imaging features. Each of these conditions presents with specific radiologic patterns and findings that can be identified through careful examination and comparison. It is essential to have a deep knowledge of the imaging characteristics associated with interstitial lung diseases in order to differentiate LC from other similar conditions effectively.

By leveraging the high resolution and sensitivity of HRCT, an accurate and timely diagnosis of lymphangitic carcinomatosis can be achieved. This accuracy is vital not only for the confirmation of LC but also for ruling out other potential conditions that may mimic its presentation. Consequently, HRCT plays a central role in guiding the clinical management and therapeutic strategies for patients suspicious for LC. The ability to accurately identify and differentiate LC from other interstitial lung diseases ensures that patients receive the most appropriate and effective treatment, ultimately improving clinical outcomes and quality of life.(14)

Early recognition of LC through characteristic radiologic findings is crucial for timely diagnosis and intervention. The integration of clinical, imaging, and pathological data is essential to arrive at a definitive diagnosis, guiding appropriate therapeutic interventions. This comprehensive approach enhances diagnostic accuracy, aiding in choosing the most effective oncological treatment strategies.(2)