Lung Metastases Imaging 

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.

See the images of pulmonary metastases below.

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%.

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.

Frequency of pulmonary metastases

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 Table 1, below).

Table 1. Incidence of Pulmonary Metastases According to Site (Open Table in a new window)

For patient education information, see the Cancer and Tumors Center, as well as Understanding Lung Cancer Medications.

Standard chest radiography (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.

In one study, the authors suggested that any patients with a suspected soft tissue sarcoma should have a CXR at presentation, followed by a CT of the chest in patients with an abnormality on CXR and routinely in patients who have large, deep-seated, or high- or intermediate-grade tumors, as well as in histologic subtypes where the incidence of lung metastases is known to be high. According to the investigators, this strategy will detect 93% of all chest metastases.^[1]

Radiographs of lung metastases are depicted in the images below.

Patterns of disease

Pulmonary metastases are usually multiple; they vary in size from 3 mm to 15 cm or more. 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 the images below.)

Nodules smaller than 2 cm are often round and have smooth margins. Larger nodules, especially metastatic adenocarcinomas 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 first two images below) than in the lower ones. Multiple cavitating masses may be the result of nonmalignant causes, such as Wegener granulomatosis (see third image below).

Calcification is seen in metastases from osteogenic sarcoma, synovial sarcoma, or chondrosarcoma (see the image below). 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 the images below).

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 high-resolution CT (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 the images below). 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 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 chest radiography (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 the images below). 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.^{[1, 2, 3, 4, 5, 6, 7, 8]}

In one study, the authors suggested that any patients with a suspected soft tissue sarcoma should have a CXR at presentation, followed by a CT of the chest in patients with an abnormality on CXR and routinely in patients who have large, deep-seated, or high- or intermediate-grade tumors, as well as in histologic subtypes where the incidence of lung metastases is known to be high. According to the investigators, this strategy will detect 93% of all chest metastases.^[1]

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.

High-resolution CT (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.^{[9, 10]}

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 the images below), 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 the first image below). 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. In rare cases, spontaneous pneumothorax can complicate lymphangitis (see second and third Images below).

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.

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.^[11]

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.

According to one study, conventional turbo spin-echo (TSE) sequences are more sensitive in depicting pulmonary metastases than single-shot TSE or 3D gradient-echo sequences.^[12]

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 chest radiography 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.^{[13, 14, 15, 16]}

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.^{[17, 18, 19]}

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.