Background: The lungs are one of the most common targets for metastatic disease. Most pulmonary metastases are nodular, but a significant minority is interstitial. Lymphangitis carcinomatosis (LC) refers to the diffuse infiltration and obstruction of pulmonary parenchymal lymphatic channels by tumor. Various neoplasms can cause lymphangitic carcinomatosis, but 80% are adenocarcinomas. The most common primary sites are the breast, lungs, colon, and stomach. Other sources include the pancreas, thyroid, cervix, prostate, larynx, and metastatic adenocarcinoma from an unknown primary cancer.
Pathophysiology: LC occurs as a result of the initial hematogenous spread of tumor to the lungs, with subsequent malignant invasion through the vessel wall into the pulmonary interstitium and lymphatics. Tumor then proliferates and easily spreads through these low-resistance channels. Less commonly, direct infiltration occurs as a result of contiguous mediastinal or hilar lymphadenopathy or an adjacent primary bronchogenic carcinoma.
Histopathologic examination reveals interstitial edema, tumor cells, and interstitial fibrosis secondary to a desmoplastic reaction as a result of tumor extension into adjacent pulmonary parenchyma. Metastatic adenocarcinoma accounts for 80% of cases.
Mortality/Morbidity: The prognosis for patients with LC is poor. Most patients survive only weeks or months.
Age: Most patients are middle-aged adults.
Anatomy: The pulmonary lymphatics are located in the interstitial components of the lung. These involve the axial (peribronchovascular and centrilobular) and peripheral (interlobular and subpleural) compartments.
Clinical Details: The usual presenting complaint is of breathlessness in a patient with known malignancy. Occasionally, patients may have a dry cough or hemoptysis. Symptoms often precede the development of any radiographic abnormality.
Preferred Examination: Plain chest radiography is the initial investigation of choice in patients presenting with any respiratory symptoms, and this examination is used in staging most cancers. However, the sensitivity of chest radiography in the detection of lymphangitic carcinomatosis is only approximately 25%.
In the appropriate clinical circumstances or when the chest radiographic findings are equivocal, the next investigation is high-resolution computed tomography (HRCT). Although the HRCT appearances of LC are nonspecific, the observation of certain features (see CAT Scan) in a symptomatic patient with an appropriate history of malignancy is highly suggestive of LC, and further investigation is generally not required.
Fragmented scintigraphic perfusion defects have been reported in LC, as have ventilation-perfusion (V/Q) mismatches. However these features are not reliable in the diagnosis of LC.
Limitations of Techniques: The radiographic features of LC are essentially nonspecific, with a diagnostic accuracy of 23%. Furthermore, chest radiographic findings are normal in as many as 50% of patients with histologic evidence of disease.
In comparison, HRCT has higher sensitivity, although the findings may not be diagnostic, as with radiography. The differential diagnosis includes other malignant conditions, such as lymphoma and Kaposi sarcoma, as well as benign entities such as sarcoidosis.
With LC, perfusion defects on a V/Q scan are nonspecific and are also described in various pulmonary pathologies, the most important of which is pulmonary embolism.
Kaposi Sarcoma, Thoracic
Kaposi sarcoma, pulmonary
Findings: On radiographs, LC appears as reticular or reticulonodular opacification, often with associated septal lines (Kerley A and B lines), peribronchial cuffing, pleural effusions, and mediastinal and/or hilar lymphadenopathy (20-50% of cases).
Degree of Confidence: Chest radiographic findings can be entirely normal. The accuracy of chest radiography is only 23%.
False Positives/Negatives: Chest radiographic findings are normal in most patients with LC. A false-positive diagnosis may occur with other interstitial lung diseases.
Findings: HRCT findings include the following: irregular, nodular, and/or smooth interlobular septal thickening; thickening of the fissures due to involvement of the lymphatics concentrated in the subpleural interstitium; preservation of normal parenchymal architecture at the level of the secondary pulmonary lobule; peribronchovascular thickening; centrilobular peribronchovascular thickening, which predominates over interlobular septal thickening in a minority of patients; polygonal arcades or polygons with prominence of the centrilobular bronchovascular bundle in association with interlobular septal thickening (50%); mediastinal and/or hilar lymphadenopathy (30-50%); and pleural effusions (30-50%).
Findings may be unilateral or bilateral, focal or diffuse, and symmetric or asymmetric. Focal unilateral disease accounts for 50% of cases. This pattern is associated in particular with underlying bronchogenic carcinoma. All of the changes described above are often associated with nodular opacities.
Degree of Confidence: Although the HRCT appearances of LC are nonspecific, the development of HRCT features in a symptomatic patient with an appropriate history of malignancy is highly suggestive of LC, and further investigation is usually not required.
False Positives/Negatives: LC may not be recognized in the presence of normal chest x-ray findings. HRCT findings of LC are also nonspecific and may be misinterpreted.
The differential diagnosis of LC includes sarcoidosis and other chronic interstitial lung diseases such as silicosis, coal worker's pneumoconiosis, extrinsic allergic alveolitis (hypersensitivity pneumonitis), and cryptogenic fibrosing alveolitis, as well as other neoplasms such as lymphoma and Kaposi sarcoma. Most of these diagnoses can be excluded on the basis of the clinical findings alone. The relative absence of polygons and the presence of architectural distortion at the level of the secondary pulmonary lobule strongly suggest fibrosis rather than LC.
Furthermore, parenchymal involvement in sarcoidosis is typically more central and/or perihilar and more bilaterally symmetric than in LC. LC never appears as honeycombing, and sarcoid granulomas are often subpleural.
Findings: Fragmented scintigraphic perfusion defects have been reported in LC, as have V/Q mismatches. However, these features are not reliable in the diagnosis of LC.