AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

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• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Nuclear Medicine
• Intervention
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

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• Introduction
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• Radiograph
• CT SCAN
• Mri
• Ultrasound
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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.

For excellent patient education resources, visit eMedicine's Cancer and Tumors Center. Also, see eMedicine's patient education articles Lung Cancer and Understanding Lung Cancer Medications.

Pathophysiology

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.

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

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.

• Patients with carcinoma of the pancreas and bronchus who have pulmonary metastases have a 5-year survival rate of less than 5% (see Images 1-2).
• 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.

Anatomy

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.

Clinical Details

As many as 90% of patients with lung metastases have a known extrathoracic primary tumor or symptoms of a synchronous primary tumor.

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 3).

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

CXR 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 CXR; these are best identified through HRCT scanning.

DIFFERENTIALS

Section 3 of 11  

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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.

RADIOGRAPH

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Findings

As mentioned above, standard CXR is usually the initial modality for detecting pulmonary metastases. More lesions are detected with a high-kilovoltage technique (>125 kV) than with the standard one.

Patterns of disease

Pulmonary metastases are usually multiple; they vary in size from 3 mm to 15 cm or more (see Images 4-9). Metastatic pulmonary nodules of the same size are believed to originate at the same time, in a single shower of emboli, and are found most commonly in the outer third of the lungs, especially in the subpleural regions of the lower zones. Rarely, numerous tiny nodules mimic the pattern of miliary tuberculosis (see Image 10).

Nodules smaller than 2 cm are often round and have smooth margins (see Image 9). Larger nodules, especially metastatic adenocarcinomas (see Image 4), are frequently lobulated and have irregular margins; they may become confluent with adjacent masses, resulting in a multinodular mass.

Cavitation occurs in 4% of metastases and 9% of primary tumors and is most frequently found in squamous cell tumors. This condition is more common in the upper lobes of the lung (see Images 11-12) than in the lower ones. Multiple cavitating masses may be the result of nonmalignant causes, such as Wegener granulomatosis (see Image 13).

Calcification is seen in metastases from osteogenic sarcoma, synovial sarcoma, or chondrosarcoma (see Image 14). These tumors may mimic hamartomas or granulomas. In rare instances, calcification may develop at the site of pulmonary metastases (typically from a testicular primary site) that appear to have vanished after chemotherapy.

Hemorrhagic metastases, with a halo of hazy opacity, are most often seen in choriocarcinoma but occasionally also appear with other vascular tumors, such as angiosarcoma or renal cell carcinoma. Metastases from teratoma of the testis may show complete fibrosis or necrosis after chemotherapy. Thin-walled air cysts, which contain no viable tumor, are present at the site of a treated metastasis (see Images 15-16).

Solitary nodules

Solitary pulmonary metastases are uncommon, accounting for 2-10% of all solitary nodules. The primary lesions that are most likely to produce solitary metastases include carcinoma of the colon; osteosarcoma; carcinoma of the kidney, testicle, or breast; and malignant melanoma. Carcinoma of the colon, especially from the rectosigmoid area, accounts for one third of cases associated with a solitary pulmonary metastasis.

There are usually no reliable features to distinguish a solitary metastatic nodule from a primary pulmonary carcinoma on CXR images or CT scans. On HRCT scans, approximately one half of metastatic nodules demonstrate irregular margins. They may be round or oval, or they may have lobulated margins. Irregular margins with spiculation may be caused by a desmoplastic reaction or tumor infiltration into the adjacent lymphatics or bronchovascular margin.

The ability to distinguish between a new primary tumor and a metastatic one has important prognostic and therapeutic implications. Resection of a solitary metastasis (or, indeed, multiple ones) may be beneficial. In addition, the interval between the appearance of the initial tumor and that of the solitary nodule is relevant; an interval of longer than 5 years in patients with osteosarcoma is more likely to be associated with a new primary tumor. However, in patients with carcinoma of the breast or kidney, pulmonary metastases may occur many years after the primary tumor is diagnosed.

Lymphangitis carcinomatosis

Although lymphangitic spread can be caused by any malignant neoplasm, it most commonly results from tumors originating in the breast, stomach, pancreas, lung, or prostate. This phenomenon is also caused by primary pulmonary carcinoma, especially small cell carcinoma and adenocarcinoma. Lymphangitic spread is present in 35% of the autopsies of patients with solid tumors. Associated pleural involvement is common.

Microscopically, malignant cells are readily seen in lymphatic cells and interlobular septa. Edema or a desmoplastic reaction can contribute to interstitial thickening. The typical radiographic pattern consists of thickened interlobular septa (5-10 mm or smaller) and bronchovascular markings of irregular contour (see Images 17-18). The pattern is more obvious in the lower lobes of both lungs. A nodular component from intraparenchymal extension may be associated with lymphangitis carcinomatosis. Hilar and mediastinal lymphadenopathy are present in 20-40% of patients, and pleural effusions are present in 30-50%. Early diagnosis of lymphangitis carcinomatosis can be difficult with CXR findings, which may be normal in 30-50% of proven cases. As previously stated, however, it can be identified at an early stage using HRCT scanning.

Intravascular emboli

Intravascular emboli occur most commonly with hepatocellular carcinoma and adenocarcinoma of the breast or stomach and may be associated with lymphangitis carcinomatosis. CXR findings may be normal. Pulmonary hypertension resulting from thromboemboli should be considered in the differential diagnosis of intravascular emboli.

Bronchial and tracheal metastases

Patients with bronchial and tracheal metastases may present with obstructive pneumonitis, wheezing, hemoptysis, and coughing. Tracheal metastases are rare.

Degree of Confidence

CXR images often fail to depict pulmonary metastatic lesions smaller than 7 mm, particularly those in the lung apices and bases or adjacent to the heart, mediastinum, and pleura. Compared with CT scans, CXR depicts fewer small metastases, and a solitary metastasis demonstrated on a CXR image is often associated with additional smaller lesions on CT scans. As previously mentioned, CXR images may fail to depict lymphangitis carcinomatosis.

False Positives/Negatives

Benign lesions, such as hamartoma, granuloma (eg, tuberculosis, histoplasmosis, Wegener granulomatosis), pulmonary abscess, infarct, and focal fibrosis, may mimic a solitary metastasis, as can a primary bronchial neoplasm.

Benign nodules, such as granulomata, abscess, multiple infarcts, and sarcoidosis, may be mistaken for metastases. Miliary metastases may appear identical to miliary tuberculosis.

Lymphangitis carcinomatosis may be mistaken for pulmonary edema and fibrosis. Pulmonary hypertension resulting from thromboembolic disease may mimic disease caused by intravascular emboli.

CT SCAN

Section 5 of 11  

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• CT SCAN
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Findings

CT scanning has become the modality of choice for the detection of metastatic tumor and for surgical planning and follow-up in patients with pulmonary metastases. Greater sensitivity over CXR or linear tomography (which CT has replaced) results from the lack of superimposition of structures and the higher contrast resolution of soft-tissue nodules in the lung parenchyma (see Images 19-22). In particular, lesions in the apices and bases or those adjacent to the heart, mediastinum, and pleura may not be seen on CXR images; however, they are seen on CT scans.

Technique

Multisection CT is the CT technique of choice for detecting pulmonary metastases. It is much faster and more sensitive than the older spiral CT and has largely replaced it.

HRCT is the technique of choice for evaluating lymphangitis carcinomatosis; using this modality, 1- to 2-mm-thick sections are obtained every 10 mm through the chest. Spatial resolution is maximized by the narrow collimation (1-2 mm) and high-resolution reconstruction algorithms.

Pulmonary nodules

Although CT scans can depict 3-mm nodules, whereas CXR images rarely show lesions smaller than 7 mm, CT's sensitivity is achieved at the cost of specificity. Many of the additional small nodules revealed by CT scans are granulomas and not metastases. Most lesions smaller than 7 mm cannot be characterized on CT scans because they are not palpable at surgery, and they cannot be examined at biopsy. The specificity of CT scanning depends on the type and stage of the primary malignancy and on the incidence of benign nodules in the population.

Various features are more likely to be associated with pulmonary metastases than with benign disease:

• Noncalcified lesions
• Spherical or ovoid lesions rather than linear or irregular ones
• Lesions that are in close relationship to an adjacent vessel
• Lesions with decreased attenuation distally
• Lesions with reticular changes

The growth of a pulmonary nodule also is a reliable indicator of metastatic disease. Doubling times of metastases range from 2 to 10 months.

Intravascular emboli are seen on histologic analysis, but they are usually not visualized on CT scans because they tend to occur in arterioles or small arteries. Rarely, they can be seen as beaded thickening of the peripheral arteries.

In highly vascular tumors, such as angiosarcoma and choriocarcinoma, HRCT scans in rare cases may depict a halo of ground-glass attenuation surrounding the metastatic nodules.

Indications for CT Scanning

Indications for CT scanning depend on the CXR findings, the likelihood that the underlying neoplasm has spread to the lungs, and the probable impact of the findings on treatment.

If CXR images demonstrate several metastases, CT scans are not required to show additional lesions. If CXR findings are normal in patients with teratoma or osteosarcoma and without metastatic disease elsewhere, the discovery of pulmonary metastases may alter the patient's treatment. If CXR images depict a solitary metastasis or surgical resection of the pulmonary metastasis is being contemplated, CT scanning is indicated.

CT scans are recommended every 3-6 months for 2 years in patients with high-risk tumors, bone and soft-tissue sarcomas, testicular teratomas, and choriocarcinomas.

Lymphangitis carcinomatosis

Although lymphangitic spread can be caused by any malignant neoplasm, it most often comes from tumors originating in the breast, stomach, lung, pancreas, or prostate. Lymphangitic spread can also arise from a primary pulmonary carcinoma, especially small cell carcinoma and adenocarcinoma (see Images 23-26), and is present in 35% of autopsies of patients with solid tumors.

HRCT is the imaging modality of choice for lymphangitis carcinomatosis; diagnosis with CXR can be difficult because findings may be normal in 30-50% of proven cases. Smooth or nodular thickening of interlobular septa and the peribronchovascular interstitium is present on HRCT scans, and normal lung architecture is preserved (see Image 27). The nodular beaded septa found in lymphangitis carcinomatosis are not seen in pulmonary fibrosis or edema. Pleural effusions may be present in as many as 50% of patients with lymphangitis, and hilar and mediastinal lymphadenopathy may occur in 20-40%. Asymmetrical tumors are present in 50% of patients, and unilateral changes are common in patients with primary bronchial carcinoma (see Image 25). In rare cases, spontaneous pneumothorax can complicate lymphangitis (see Images 28-29).

Degree of Confidence

CT scan findings are not specific and cannot help in distinguishing between metastases and such benign lesions as granulomas and pulmonary lymphoid nodules. The specificity of CT scans is higher in areas in which granulomata are uncommon.

The greater the sensitivity of CT scanning (ie, multisection CT and spiral CT modalities), the lower its specificity, because a larger number of benign nodules are detected. This is especially true in regions of the world where histoplasmosis is endemic.

False Positives/Negatives

Nodules smaller than 3 mm are often missed on CT scans. False-positive results may be caused by hamartomas, granulomas (resulting from tuberculosis, histoplasmosis, Wegener granulomatosis), sarcoidosis, silicosis, small infarcts, small areas of fibrosis, and intrapulmonary lymph nodes. Differentiation between metastases and benign lesions may be impossible.

MRI

Section 6 of 11  

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• Mri
• Ultrasound
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• References

Findings

Spin-echo MRI with a 0.35-T magnet can depict small nodules adjacent to vessels, which often are missed on CT scans. However, nodules near the diaphragm frequently are missed on MRI studies because of respiratory motion.

Among the various MRI sequences, short-tau inversion-recovery sequences have the highest sensitivity. False-positive findings are rare with CT scanning, but they are not uncommon with MRI because of diaphragmatic motion, especially in the lower lobes. CT scanning remains the imaging modality of choice.

ULTRASOUND

Section 7 of 11  

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Findings

Ultrasonographic findings do not contribute to the diagnosis of pulmonary metastases.

NUCLEAR MEDICINE

Section 8 of 11  

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Findings

Nuclear medicine studies are usually not used as primary imaging techniques in detecting pulmonary metastases.

Fluorodeoxyglucose–positron emission tomography (FDG-PET) imaging has secured an important role in the assessment and management of a multitude of pulmonary disorders, including solitary pulmonary nodules, lung cancer, and pleural diseases. Although conventional imaging modalities, such as CXR and CT scanning, are considered essential in diagnosing these conditions, FDG-PET can provide new information and complement structural imaging techniques in the evaluation of such disorders. FDG-PET is useful in differentiating benign pulmonary nodules from malignant ones. New developments, such as prospects for the potential utility of novel radiotracers and delayed imaging, can further refine the role of FDG-PET scans in the workup of lung nodules and cancer.

The recent introduction of combined PET-CT machines will affect the future workup and treatment of patients with cancer and will also be used in radiation treatment planning. Interpretation of PET scans in the absence of correlative anatomic information can be challenging. PET-CT fusion imaging allows the correlation of findings from 2 concurrent imaging modalities in a comprehensive examination. Subtle findings from FDG-PET that might otherwise be disregarded or interpreted as physiologic variants may lead to detection of a malignant process after being correlated with simultaneously acquired CT scan findings. Equivocal CT scan findings—representing perhaps a malignant tumor, reactive changes, or fibrosis—can be clarified with the help of the additional metabolic information provided by concurrent FDG-PET.

Degree of Confidence

Most false-negative FDG-PET results are caused by micrometastases and lesions smaller than 10 mm. CT scanning is equivalent to or more sensitive than FDG-PET for detecting small pulmonary lesions.

False Positives/Negatives

Physiologic variants, benign tumors, and inflammatory diseases may all cause increased uptake of FDG and mimic malignant disease.

INTERVENTION

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Percutaneous biopsy or fine-needle aspiration may be used in certain patients to confirm the nature of suggested pulmonary metastases.

Medical/Legal Pitfalls

• Failure to detect pulmonary metastases prior to radical excision of the primary tumor
• Failure to plan and perform sequential follow-up imaging of the thorax in patients with a high risk of pulmonary metastases, such as those with teratoma of the testis or osteosarcoma

MULTIMEDIA

Section 10 of 11  

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• References

Media file 1:  Pulmonary metastases from a carcinoma of the bronchus. (See also Image 2.)
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Media file 2:  Detailed view of Image 1 shows numerous small pulmonary metastases from a carcinoma of the bronchus.
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Media file 3:  Small right pneumothorax from pulmonary metastases caused by Ewing sarcoma.
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Media file 4:  Large (cannonball) lung metastases from renal cell carcinoma.
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Media file 5:  Lung metastases from a low rectal carcinoma.
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Media file 6:  Pulmonary metastases from carcinoma of the breast. Note the right mastectomy and pleural effusion.
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Media file 7:  Multiple pulmonary metastases from an osteosarcoma.
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Media file 8:  Close-up view of pulmonary metastases (in the same patient as in Image 7). The right scapula had been excised because of an osteosarcoma.
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Media file 9:  Numerous pulmonary metastases from a carcinoma of the cecum.
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Media file 10:  Miliary shadowing caused by pulmonary metastases.
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Media file 11:  Pulmonary metastasis from squamous cell carcinoma of the anus shows central cavitation.
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Media file 12:  Pulmonary metastasis from squamous cell carcinoma of the anus shows central cavitation. This lateral view was obtained in the same patient as in Image 11.
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Media file 13:  Lung metastases. Cavitating masses caused by Wegener granulomatosis.
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Media file 14:  Calcification (arrowhead) in a pulmonary metastasis from a chondrosarcoma.
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Media file 15:  Pulmonary metastasis from teratoma of the testis before chemotherapy.
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Media file 16:  Pulmonary metastasis from a teratoma of the testis (in the same patient as in Image 15) after chemotherapy, shows fibrosis or necrosis of the tumor.
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Media file 17:  Lung metastases. Lymphangitis carcinomatosa from carcinoma of the prostate. Note the sclerotic bony metastases. (See also Image 18.)
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Media file 18:  Detailed view of Image 17 shows lymphangitis carcinomatosa from carcinoma of the prostate.
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Media file 19:  Solitary, 10-mm pulmonary metastasis (arrowhead) from a renal cell carcinoma, which was not visible on chest radiographs.
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Media file 20:  Multiple pulmonary metastases and pleural effusions from a carcinoma of the rectum.
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Media file 21:  Pulmonary metastases are usually more numerous in the lower zones than in the upper ones. (See also Image 22.)
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Media file 22:  Pulmonary metastases are less numerous in the upper zones. (Image obtained in same patient as in Image 21.)
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Media file 23:  Lung metastases. Unilateral lymphangitis carcinomatosa from bronchial carcinoma in the right hilum. (See also Image 24.)
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Media file 24:  Detailed view of Image 23 shows unilateral lymphangitis carcinomatosa caused by bronchial carcinoma in the right hilum.
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Media file 25:  CT scan shows unilateral lymphangitis in a patient with bronchial carcinoma (in the same patient as in Image 23).
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Media file 26:  CT scan demonstrates underlying bronchial carcinoma with narrowing of the right main bronchus (in the same patient as in Image 23).
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Media file 27:  High-resolution CT scan demonstrates irregular, coarse thickening of the interlobular septa caused by lymphangitis carcinomatosa from a renal cell carcinoma. Note the bilateral pleural effusions.
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Media file 28:  Lung metastases. Lymphangitis from breast carcinoma. (See also Image 29.)
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Media file 29:  Lymphangitis from breast carcinoma. This right tension pneumothorax occurred 6 weeks after Image 28 was obtained. Note the large left pleural effusion.
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REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Differentials
• Radiograph
• CT SCAN
• Mri
• Ultrasound
• Nuclear Medicine
• Intervention
• Multimedia
• References

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Article Last Updated: Oct 25, 2006