Introduction
Small right pneumothorax from pulmonary metastases caused by Ewing sarcoma.
Large (cannonball) lung metastases from renal cell carcinoma.
Pulmonary metastasis from teratoma of the testis before chemotherapy.
Background
Pulmonary metastases are common and most frequently occur with tumors that have rich systemic venous drainage. Examples of such metastases include renal cancers, bone sarcomas, choriocarcinomas, melanomas, testicular teratomas, and thyroid carcinomas. Most pulmonary metastases arise from common tumors, such as breast, colorectal, prostate, bronchial, head-and-neck, and renal cancers. The detection of pulmonary metastases is crucial in the treatment of patients with cancer.
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Frequency
United States
Autopsy series have demonstrated that pulmonary metastases are present in 20-54% of all patients who die of cancer. The incidence of pulmonary metastases during the course of the cancer or at presentation is less than that of the autopsy series and varies with the primary neoplasm (see the table below).
Incidence of Pulmonary Metastases According to Site
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Table
| Primary Tumor | Frequency at Presentation, % | Frequency at Autopsy, % |
| Choriocarcinoma | 60 | 70-100 |
| Melanoma | 5 | 66-80 |
| Testis, germ cell | 12 | 70-80 |
| Osteosarcoma | 15 | 75 |
| Thyroid | 7 | 65 |
| Kidney | 20 | 50-75 |
| Head and neck | 5 | 15-40 |
| Breast | 4 | 60 |
| Bronchus | 30 | 40 |
| Colorectal | <5 | 25-40 |
| Prostate | 5 | 15-50 |
| Bladder | 7 | 25-30 |
| Uterus | <1 | 30-40 |
| Cervix | <5 | 20-30 |
| Pancreas | <1 | 25-40 |
| Esophagus | <1 | 20-35 |
| Stomach | <1 | 20-35 |
| Ovary | 5 | 10-25 |
| Hepatoma | <1 | 20-60 |
| Primary Tumor | Frequency at Presentation, % | Frequency at Autopsy, % |
| Choriocarcinoma | 60 | 70-100 |
| Melanoma | 5 | 66-80 |
| Testis, germ cell | 12 | 70-80 |
| Osteosarcoma | 15 | 75 |
| Thyroid | 7 | 65 |
| Kidney | 20 | 50-75 |
| Head and neck | 5 | 15-40 |
| Breast | 4 | 60 |
| Bronchus | 30 | 40 |
| Colorectal | <5 | 25-40 |
| Prostate | 5 | 15-50 |
| Bladder | 7 | 25-30 |
| Uterus | <1 | 30-40 |
| Cervix | <5 | 20-30 |
| Pancreas | <1 | 25-40 |
| Esophagus | <1 | 20-35 |
| Stomach | <1 | 20-35 |
| Ovary | 5 | 10-25 |
| Hepatoma | <1 | 20-60 |
International
The incidence of pulmonary metastases reflects the prevalence of primary tumors in the table above (see Frequency, United States), and no international variation is reported.
Mortality/Morbidity
The presence of pulmonary metastases is a bad prognostic factor that indicates disseminated disease. Mortality depends on the primary tumor.
Pulmonary metastases from a carcinoma of the bronchus. (See also Image below.)
Detailed view of Image above shows numerous small pulmonary metastases from a carcinoma of the bronchus.
- Patients with carcinoma of the pancreas and bronchus who have pulmonary metastases have a 5-year survival rate of less than 5% (see Images above and Images 1-2 in Multimedia).
- One half of the patients with lymphangitis carcinomatosis die within 3 months.
- Chemosensitive tumors, such as choriocarcinoma and testicular teratoma, have a better prognosis.
- An isolated pulmonary metastasis (eg, from colon or kidney) can be resected, with a 5-year survival rate of 50%.
Sex
The incidence of pulmonary metastases reflects the incidence of common primary carcinomas. Overall, there is no significant difference between affected males and females.
Age
The incidence of common tumors increases with patient age, as does the frequency of pulmonary metastases. However, pulmonary metastases can also be seen in children with neoplasms, such as Wilms tumors.
Presentation
Natural history and presentation
Pulmonary metastases are common because the entire output of the right heart and the lymphatic system flow through the pulmonary vascular system.
The initial event occurs at the primary tumor site. Fragments of tumor are dislodged after venous invasion, and they are carried as tumor emboli to the lungs via the systemic circulation. The majority of these fragments lodge in the small pulmonary arteries or arterioles, where they may proliferate and extend into the lung parenchyma and ultimately form nodules. These nodules are most commonly located either subpleurally or in the lung bases rather than in the upper lung, locations that reflect the pulmonary arterial circulation.
Less often, tumor emboli remain confined to the perivascular interstitium and spread along the lymphatic channels toward the hilum or lung periphery. This is the mechanism in most patients with lymphangitis carcinomatosis. The second, and less common, mechanism is retrograde spread from hilar lymph nodes via lymphatic channels.
Pulmonary nodules are the most common manifestation of secondary neoplastic disease in the lungs. They are usually derived from tumor emboli that arise from invasion of tumor capillaries. The tumor emboli drain via the systemic veins and pulmonary arteries, subsequently lodging in the small pulmonary arteries or arterioles and extending into adjacent lung tissue. Pulmonary nodules are usually multiple, spherical, and variably sized. Metastases that occur via bronchial arteries, pulmonary lymphatics, and transbronchial aspiration, as well as across the pleural cavity, are less common.Lymphangitis carcinomatosis is most often caused by breast, lung, stomach, pancreatic, or prostate cancer. It usually results from hematogenous metastases to small pulmonary capillaries, with secondary invasion of the peripheral pulmonary lymphatics. Retrograde extension from hilar or mediastinal nodes or direct invasion from diaphragmatic lymphatics is less common. Endobronchial metastases, which are rare, are associated with tumors of the breast, colon, and kidney, as well as with sarcoma and melanoma.
As many as 90% of patients with lung metastases have a known extrathoracic primary tumor or symptoms of a synchronous primary tumor.Symptoms
Symptoms are usually absent in patients with multiple metastases (80-95%). Dyspnea may develop as a result of parenchymal replacement by a large tumor load, airway obstruction, or pleural effusion. Sudden dyspnea is associated with the rapid development of a pleural effusion, pneumothorax, or hemorrhage into a lesion.
Although the lung metastases themselves may be asymptomatic, patients often have symptoms related to their primary tumor (eg, renal cell carcinoma, colorectal tumors, breast cancer). When lung metastases are discovered in patients with no symptoms suggestive of a primary site, then clinically silent tumors, such as pancreatic or biliary tumors, should be considered.
Patients with lymphangitis carcinomatosis usually have progressive dyspnea and a dry cough. Endobronchial metastases may result in wheezing or hemoptysis. Metastatic extension to the pleura can cause pleuritic pain, and an apical metastasis may lead to Pancoast syndrome. Hypertrophic pulmonary osteoarthropathy is rare. Pneumothorax is an uncommon complication in patients with pulmonary metastases, except in those with osteosarcoma as the primary site. In the latter case, up to 5% of patients may develop a pneumothorax, more often during chemotherapy than at other times (see Image below and Image 3 in Multimedia).
Percutaneous biopsy or fine-needle aspiration may be used in certain patients to confirm the nature of suggested pulmonary metastases.
Small right pneumothorax from pulmonary metastases caused by Ewing sarcoma.
Preferred Examination
Chest radiography (CXR) is usually the first examination performed to detect pulmonary metastases. Also, metastases may be unexpectedly discovered on CXR examination.
Computed tomography (CT) scanning has higher resolution than CXR, revealing more and smaller nodules than the other technique does.
High-resolution CT (HRCT) is the modality of choice for demonstrating the presence and extent of lymphangitis carcinomatosis.
Transthoracic biopsy and needle aspiration may be helpful in determining the nature of the nodules. Small tissue fragments can be compared with those of the known primary tumor. Transthoracic needle aspiration has a positive yield of 85-95% in the evaluation of pulmonary nodules, but the yield is lower with lymphangitic tumor spread, which usually requires transbronchial biopsy or thoracoscopic wedge resection for the histologic diagnosis.
Sputum cytologic analysis findings of malignant cells or bronchial brushings may be positive in 35-50% of patients with pulmonary metastases. Cytologic analysis of any pleural fluid of malignant origin may yield positive results in as many as 50% of patients. Such analysis usually does not distinguish between primary and secondary malignant lesions; it does this most easily for renal and colonic metastases.
Bronchoscopy may be a useful examination in assessing pulmonary metastases with endobronchial extension.
Limitations of Techniques
Chest radiography often reveals only a single pulmonary metastasis even when more than one such lesion is present. CT scanning is more appropriate for identifying multiple pulmonary metastases, being better able to detect lesions smaller than 10 mm in diameter.
The early stages of lymphangitis carcinomatosis are difficult to diagnose with chest radiography; these are best identified through high-resolution CT (HRCT) scanning.
Differential Diagnoses
Other Problems to Be Considered
Conditions to consider in the differential diagnosis of a solitary nodule include benign lesions, such as hamartoma, granuloma (eg, tuberculosis, histoplasmosis, Wegener granulomatosis), pulmonary abscess, infarct, focal fibrosis, and primary bronchial neoplasm.
Conditions to consider in the differential diagnosis of multiple nodules, which are more likely than single lesions to be metastases, include granulomata, abscess, multiple infarcts, and sarcoidosis.
Conditions to consider in the differential diagnosis of lymphangitis carcinomatosis include pulmonary edema and fibrosis.
More on Lung, Metastases |
 Overview: Lung, Metastases |
| Imaging: Lung, Metastases |
| Follow-up: Lung, Metastases |
| Multimedia: Lung, Metastases |
| References |
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Further Reading
Keywords
pulmonary metastases, lymphangitis carcinomatosis, pulmonary secondaries, lung secondaries, secondary lung neoplasms, lung cancer, lung malignancies, renal cancers, bone sarcomas, choriocarcinomas, melanomas, testicular teratomas, thyroid carcinomas, lung hamartoma, thoracic histoplasmosis, thoracic Hodgkin disease, thoracic lung cancer, non–small cell lung cancer, NSCLC, pulmonary hypertension, thoracic sarcoidosis
