Metastatic tumors in the lung: A practical approach to diagnosis

Vascular metastases

Hematogenous spread is the most common form of pulmonary metastasis as the lungs receive the entire cardiac output and contain a huge capillary bed. The detailed principles underlying vascular metastasis have been outlined elsewhere. Malignant tumors may contain clones of cells with differing metastatic potential with some clones acquiring the ability to enter the bloodstream as microemboli. At selected distant sites, these malignant clonal cells adhere to the endothelial basement membranes and extravasate into the extracellular matrix to form metastatic deposits. In this paradigm, a micrometastasis proliferates to yield a larger mass, which later, often as long as several years, may become visible radiographically or be associated with clinical signs and/or symptoms. Most pulmonary metastases show nests of neoplastic cells surrounded by a variable quantity of fibrous stroma. At this stage, no malignant cells typically are found in the pulmonary arterial, venous, or capillary system unless they arrive later in a newer microembolus.

The rate at which potentially metastasizing cellular subclones develop in primary tumors varies considerably. The probability that such lesions will spread hematogenously depends on both tumor-related factors and conditions in the milieu of the host tissues. Some malignancies, such as osteosarcoma, often shed micrometastases before the primary tumor is detected clinically. Other tumors may show metastasis only very late in their biologic evolution.

The clinical presentation of patients with hematogenous pulmonary metastases is variable. Many patients have no symptoms and lesions are detected only through imaging studies undertaken for cancer staging purposes or for surveillance during cancer treatment. The radiographic appearance of a metastatic malignancy to the lung may show a single central or peripheral mass, multiple central or peripheral masses, diffuse infiltrates, or a combination of the latter two possibilities. Metastases tend to manifest as having smooth or rounded contours radiographically in contrast to much more irregular shapes of primary carcinomas. If a patient is symptomatic, the clinical findings reflect the location and extent of the metastatic deposits and commonly include chest pain, dyspnea, cough, hemoptysis, and wheezing.

In addition to microembolization, extrapulmonary tumors may spread to the lungs as macroscopic emboli that involve large or medium-sized pulmonary arteries. Large-vessel tumor emboli may cause acute heart failure, sudden death, rapidly evolving pulmonary hypertension, and pulmonary infarcts. The tumors that most commonly give rise to macroscopic emboli are those associated with major systemic veins (e.g., renal or hepatic carcinomas invading the renal and hepatic veins) and primary tumors of the heart (myxomas and sarcomas).

In rare cases, hematogenous spread consists of tumor-related thrombotic pulmonary microangiopathy ^, with occlusive luminal tumor plugs in arterioles and capillaries without interstitial involvement or the formation of masses. Neoplasms that may show this pattern of metastatic spread include carcinomas of the breast, gastrointestinal tract, liver, pancreas, uterus, gallbladder, prostate gland, and ovary. Soares et al. reported that most malignant tumors that occlude small pulmonary vascular channels also may contain malignant cells within larger vessels. Patients with metastatic microvascular occlusion typically present with severe pulmonary hypertension, progressive dyspnea, and cor pulmonale. ^,

As a general rule, all caval venous blood flows through the lungs, and portal venous return passes through the liver. Consequently, depending on the primary site of the tumor, metastases preferentially are seen in one of these two organs. Malignant neoplasms that arise in sites with other pathways of vascular drainage (e.g., prostatic tumors preferentially shed into the paravertebral venous plexus) infrequently involve the lungs secondarily. Arterially borne metastases to the lungs are relatively rare and are usually mediated by the bronchial arteries. The most common source of such lesions is a primary lung cancer that has gained access to the pulmonary venous system.

Hematogenous metastasis in the lung is associated with a spectrum of radiologic findings. The most common roentgenographic appearance is that of multiple, bilateral, and variably sized masses ( Figs. 18.1–18.3 ). A solitary intraparenchymal nodule occasionally is seen. The metastatic implants usually appear in the mid- to lower lung fields, where the parenchymal perfusion is greatest. In up to 90% of patients with bilateral secondary disease, the lesions are peripheral and subpleural ( Fig. 18.4 ). ^, The variability in the size of the metastatic nodules is associated with the different temporal ages of the lesions, dissimilar growth rates, and other factors. At the time of detection, secondary malignancies usually measure less than 3 to 4 cm in diameter, which is smaller than the typical primary pulmonary carcinomas. On serial radiologic examinations, metastases tend to enlarge more rapidly than primary carcinomas, excluding small cell carcinomas.

Tumors involving small vessels may produce linear parenchymal infiltrates. Patients who have both masses and metastases in small vessels or lymphatic spaces present with opacities and linear streaks. Embolic tumors in the large pulmonary arteries may show the radiographic appearance of an infarct, with a wedge-shaped peripheral zone of consolidation and a pleural effusion.

Solitary metastases in the lungs comprise up to 10% of all malignant tumors. Filderman and coworkers suggested that solitary metastatic lesions larger than 5 cm in diameter most likely originated in the breast, kidney, or soft tissue. Metastasis in the form of a solitary mass on plain films may appear as multiple contiguous or coalescent masses on computed tomography. Quint and colleagues reported that, statistically, patients with carcinomas of the head and neck, bladder, breast, cervix, bile ducts, esophagus, ovary, prostate gland, or stomach were more likely to have a solitary metastasis to the lung than a new primary bronchogenic tumor, even when a significant period had elapsed after diagnosis of the extrapulmonary neoplasms. On the other hand, patients with a history of malignant melanoma, sarcoma, or malignant germ cell tumor more likely had a second primary malignancy of the lung under the same circumstances.

Large metastatic foci may undergo cavitation or be associated with a pneumothorax or a bronchopleural fistula ( Fig. 18.5 ). The most common secondary tumor that cavitates is a squamous cell carcinoma, often originating in the head and neck and morphologically showing extensive keratinization. Metastatic sarcoma and adenocarcinoma also may exhibit cavitation. Destructive pleural growth of a metastatic tumor may cause a pneumothorax or a transpleural fistulae, seen most frequently in pediatric mesenchymal malignancies, such as an osteosarcoma.

Lymphogenous metastases

Lymphogenous metastasis accounts for 5% to 8% of pulmonary metastases, although one study reported that up to 56% of pulmonary metastases were lymphogenously mediated. Most patients with lymphatic-borne lung metastases have a poor prognosis, with 90% of patients dying within 6 months.

The radiographic appearance of lymphangitic metastasis is variable and in 50% of cases, chest x-rays show no apparent abnormality. Yang and Lin described four radiologic patterns when lymphangitic metastasis are detectable on chest x-ray :

• 1.

  Bilateral linear infiltrates without hilar enlargement or intrapulmonary masses

• 2.

  Hilar masses with centripetal parenchymal extension, seen most commonly in patients with cervical, gastric, and breast cancers ( Fig. 18.6 )

  

• 3.

  Focal linear infiltration of the parenchyma associated with a central primary tumor

• 4.

  Parenchymal radiations from a peripheral primary tumor

In first two metastatic patterns, pleural and/or hilar lymph nodal involvement may be seen. More than 90% of these cases are metastatic adenocarcinomas. It is estimated that fewer than 1% of patients with pulmonary metastases from tumors arising outside the thorax also have hilar adenopathy. Although this figure may appear low, hilar lymphadenopathy in patients with secondary pulmonary malignancies is not uncommon in absolute terms because of the high prevalence of patients with metastatic disease.

Carcinomas may gain access to the pulmonary lymphatic system by: (1) retrograde spread, (2) direct invasion of the pulmonary lymphatics, and (3) passage through adjacent blood vessels. This last process is the most common with tumor first spreading hematogenously to the lung followed by focal areas of interstitial growth. The neoplastic cells then may enter the lymphatics and permeate further throughout the lungs ( Fig. 18.7 ). Tumor in alveolar spaces may likewise be absorbed through the lymphatics adjacent to terminal bronchioles. Patients who have lymphangitic intrapulmonary metastases generally have had previous hematogenous spread. Direct lymphatic invasion is most often associated with tumors arising in the breast or stomach ^{, ,} with metastases almost exclusively detected in the pulmonary lymphatic spaces, without the formation of mases. Other metastatic carcinomas capable of showing the same pattern of spread include malignancies from the ovary, thyroid, bladder, esophagus, liver, and appendix after the development of pseudomyxoma peritonei. ^{, ,}

Direct seeding

Metastatic disease arising through direct seeding occurs when a malignant tumor gains access to a serosally lined cavity, such as the pleural space. Neoplasms that directly seed the pleura include primary lung cancers and malignancies of various lineages that originate in the chest wall or mediastinum. Primary lung tumors, such as a peripheral pulmonary carcinoma, may grow through the visceral pleura, which is less common in cases of chest wall sarcoma. The malignant carcinoma cells attach themselves to multiple pleural sites and invade the subjacent tissues. Multiple subpleural nodules may coalesce to form a large serosally-based lesion.