The lungs are the second most common site of tumor metastases. At autopsy, rates of detection of thoracic metastases from various extrathoracic tumors range from 10% to 100%. Although the rate of detection of pulmonary metastases for any tumor type throughout a patients clinical course is expected to be lower than the incidence cited in autopsy series, early detection of such metastases may affect both tumor staging and treatment planning.[3-5]
Since different types of extrathoracic malignancy spread via different pathways, they metastasize to the lungs at varying frequencies and time courses. In addition, for certain tumors, the extent of local invasion at presentation also determines the likelihood of distant metastases. Consequently, depending on tumor type and extent of local disease, different radiologic modalities may be required in order to provide optimal screening for pulmonary metastases.
Most commonly, metastatic disease to the lung is secondary to: (1) primary tumors that have a high propensity for pulmonary metastases, such as melanomas, choriocarcinomas, sarcomas, and carcinomas of the head and neck, testis, and adrenal gland, as well as certain types of thyroid cancer[2,3]; or (2) primary tumors that are somewhat less likely to metastasize to the lung but occur with high prevalence within the population, such as breast, colorectal, stomach, and pancreatic, adenocarcinomas.[2,6]
The two categories described above may be explained by differences in the mechanisms of metastasis. Several multi-step cascade processes have been described that help explain the likelihood of metastasis to each organ system.[3,7,8] An understanding of these processes suggests which radiologic modalities will be the most useful in screening for metastatic disease and where in the body screening will provide the highest rate of detection.
Depending on tumor type and location, one of three organsthe lung, liver, or boneserves as a filter for hematogenous or lymphangitic metastases. In the first group in Table 1, the lungs serve as a filter for tumors with venous drainage to this organ. These tumors metastasize first to the lungs and then to other organs, such as the liver. Sarcomas, melanomas, choriocarcinomas, thyroid and adrenal gland tumors, and carcinomas of the testes and head and neck fall into this group.
The second group consists of gastrointestinal tumors, such as adenocarcinomas of the stomach, colon, and pancreas, that are drained by the portal venous system, usually causing initial seeding to the liver. These tumors metastasize to the lungs, but do so at a more advanced stage of disease, subsequent to metastatic spread to the liver.
Tumors in the third group may simultaneously seed multiple organs, including the lungs, either via blood vessels or the lymphatics. These tumors, which metastasize to the lung less frequently than those in the first and second groups, include cancers of the bladder, ureter, kidney and female genital tract (uterus and cervix). Ovarian adenocarcinomas are the exception to this rule, seeding the lungs only after metastasizing to the liver. Of note, cancers of the bladder and female genital tract are three times more likely to seed the liver or lungs by the lymphatic route than through hematogenous spread.
The fourth pattern of metastasis is typified by prostate adenocarcinoma, a common tumor that infrequently metastasizes to the lungs. This cancer usually spreads first to the bones of the pelvis and vertebrae through the vertebral venous plexus. From the bones, metastases then spread hematogenously to the lungs and other organs.
Breast adenocarcinoma is unique in that it is not only the most common extrathoracic tumor to metastasize to the lungs but also has the most complicated pattern of metastatic spread. Breast adenocarcinoma has three possible initial routes of metastatic spread: (1) to the lungs through lymphatic channels, (2) to the liver through the abdominal lymphatic system, or (3) to the vertebrae through the intercostal veins and vertebral venous plexus. From the lungs, the tumor may then seed the liver, central nervous system (CNS), endocrine system, and appendicular skeleton.
The physician should tailor radiologic surveillance of patients with primary extrathoracic tumors to the tumor type and its pathophysiology. Radiologic tools currently available for thoracic screening for metastatic disease include the standard posterior-anterior (PA) and lateral chest radiograph, conventional and spiral thoracic computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET).
Standard Chest Radiograph
The standard PA and lateral chest radiograph is the most fundamental screening tool for pulmonary metastatic disease. It is suitable for staging and follow-up of all tumors that first metastasize to an organ system other than the lung, as long as there is no other clinical or radiographic evidence (such as on CT) of extrathoracic metastastic disease. It can also be used for the staging and follow-up of lesions that are less likely to metastasize to the lungs when not locally invasive (groups II through V in Table 1).
For tumors such as adenocarcinomas of the stomach, colon, and pancreas, screening and follow-up for thoracic metastases by standard PA and lateral chest radiograph are accurate when accompanied by a negative CT screening examination of the liver.[8,10] After demonstration of liver metastases, however, the likelihood of pulmonary metastases increases dramatically and thoracic screening should then be performed routinely by CT, if clinically indicated. Similarly, as prostate cancer is most likely to invade the bones prior to involving any other organ, thoracic screening by standard chest radiography is suitable if there is no scintigraphic demonstration of skeletal metastases.
Tumors That Simultaneously Metastasize to Lungs and Other OrgansFor renal cell, transitional cell, and most tumors of the female genital tracttumors that may simultaneously metastasize to the lungs and other organschest radiography may be used for initial screening and follow-up for pulmonary metastatic disease, with thoracic CT performed only in patients with advanced local disease, thoracic symptoms, or abnormal chest radiographic findins. Likewise, for patients with breast adenocarcinoma, which also commonly metastasizes to the lungs, liver, and bone, thoracic CT is warranted only for those with locally advanced disease (stage IIB or III). In patients with stage I or II breast cancer, in whom the yield for pulmonary metastases is low, screening by standard chest radiography is suitable, with further CT thoracic assessment performed only if a new radiographic abnormality is detected.
Chest Radiography vs Chest CTThoracic CT examinations, especially the new spiral techniques, are highly sensitive for the detection of pulmonary nodules (95% for nodules > 1 cm; 91% for nodules < 1 cm), but this high sensitivity comes at a cost of a decrease in specificity.[3,12] Consequently, for malignancies that usually do not metastasize to the lung, the yield of a thoracic CT for metastatic disease, in the absence of metastatic disease elsewhere, is low.
Although CT is clearly more thorough than standard chest radiography, it is also likely to demonstrate very small lesions (< 1 cm) that go undetected by standard chest radiography. In patients with certain tumors (as described above) who have no evidence of metastatic disease elsewhere, these small pulmonary lesions are less likely to represent metastatic disease and more likely to be benign.
It is important to note that the specificity of small subpleural nodules is age-dependent. In cancer patients, the specificity of small subpleural nodules for metastatic disease in patients less than 20 years of age is greater than 90%. In patients between the ages of 40 and 65, this specificity drops to approximately 60%.[Charles Putman, md, unpublished data, May 1988] In addition, these lesions (unless they definitively contain calcium) cannot be further characterized as benign or malignant by CT and are too small for fine-needle aspiration (FNA) biopsy.
Furthermore, one would be hesitant to perform thoracoscopy or an open thoracotomy for such a small lesion in the absence of other metastatic disease. Essentially, the discovery of a small thoracic lesion in the absence of additional metastatic disease would leave one with the dilemma as to how to proceed further, and could result in additional, likely unnecessary noninvasive or invasive testing.
Certainly, if a nodule is identified on the standard chest radiograph, prior radiographs should be obtained to determine whether or not it has been present and stable over a 2-year period. If the nodule is new, a thoracic CT should then be performed to further assess the lesion and to determine the extent of disease. A patient with an extrathoracic malignancy in whom even a single new pulmonary nodule is found on a chest radiograph may prove to have multiple lesions on thoracic CT scanning.[10,14]
1. Willis RA: The Spread of Tumors in the Human Body, pp 167-174. London, Butterworth, 1973.
2. Whitesell PL, Peters SG: Pulmonary manifestations of extrathoracic malignant lesions. Mayo Clin Proc 68:483-491, 1993.
3. Davis SD: CT evaluation for pulmonary metastases in patients with extrathoracic malignancy. Radiology 180:1-12, 1991.
4. Libshitz HI, North LB: Pulmonary metastases. Radiol Clin North Am 20:437-451, 1982.
5. Filderman AE, Coppaoe L, Shaw C, et al: The biology of metastatic disease. Invest Radiol 25:215-224, 1990.
6. Quint LE, Gross BH, Glazer GM: Primary and metastatic malignancy, in Putman CE (ed): Diagnostic Imaging of the Lung, pp 199-251. New York, Marcel-Dekker, 1990.
7. Viadana E, Bross IDJ, Pickren JW: Cascade spread of blood-borne metastases in solid and nonsolid cancers of humans, in Weiss L, Gilbert HA (eds): Pulmonary Metastasis, pp 142-167. Boston, Hall, 1978.
8. Morgan-Parkes JH: Metastases: Mechanisms, pathways, and cascades. Am J Roentgenol 164:1075-1082, 1995.
9. Temeck BK, Pass HI: Intrathoracic metastases, in Aisner J, Arrigada R, Green MR et al (eds): Comprehensive Textbook of Thoracic Oncology, pp 906-917. Baltimore, Williams and Wilkins, 1996.
10. Chiles C, Ravin CE: Intrathoracic metastasis from extrathoracic malignancy: A radiographic approach to patient evaluation. Radiol Clin North Am 23:427-438, 1985.
11. Henderson Cl: Breast cancer, in Murphy GP, Lawrence W, Lenhard RE (eds): Clinical Oncology, pp 198-219. Atlanta, American Cancer Society, 1995.
12. Buckley JA, Scott WW, Siecelman SS, et al: Pulmonary nodules: Effect of increased data sampling on detection with spiral CT and confidence in diagnosis. Radiology 196:395-400, 1995.
13. Chalmers N, Best JJ: The significance of pulmonary nodules detected by CT but not by chest radiography in tumor staging. Clin Radiol 44:410-412, 1991
14. Cahan WG, Castro EB, Hajdu SI: The significance of a solitary lung shadow in patients with colon carcinoma. Cancer 33:414-421, 1974.
15. Vanel D, Henry-Amar M., Lumbroso J, et al: Pulmonary evaluation of patients with osteosarcoma: Roles of standard radiography, tomography, CT, scintigraphy, and tomoscintigraphy. Am J Roentgenol 143:519-523, 1984.
16. Meyer JE, Stolbach L: Pretreatment radiographic evaluation of patients with malignant melanoma. Cancer 42:125-126, 1978.
17. Heaston DK, Putman CE, Rodan BA, et al: Solitary pulmonary metastases in high-risk melanoma patients: A prospective comparison of conventional and computed tomography. Am J Roentgenol 141:169-174, 1983.
18. Husband JE, Mc Donald JS, Peckham MJ: Computed tomography in testicular disease: A review. J R Soc Med 74:441-447, 1981.
19. McLoud TC, Kalisher L, Stark P, et al: Intrathoracic lymph node metastases from extrathoracic neoplasms. Am J Roentgenol 131:403-407, 1978.
20. Horsley JS, Fratkin MJ: Cancer of the thyroid and parathyroid gland, in Murphy GP, Lawrence W, Lenhard RE (eds): Clinical Oncology, pp 342-354. Atlanta, American Cancer Society, 1995.
21. Kwauk S, Burt M: Pulmonary metastases from adrenal cortical carcinoma: Results of resection. J Surg Oncol 53:243-246, 1993.
22. Probert JC, Thompson RW, Bagshaw MA: Patterns of spread of distant metastases in head and neck cancer. Cancer 33:127-133, 1974.
23. Shaha A, Strong EW: Cancer of the head and neck, in Murphy GP, Lawrence W, Lenhard RE, (eds): Clinical Oncology, pp 355-377. Atlanta, American Cancer Society, 1995.
24. Warbürg O: The Metabolism of Tumors, pp 129-169. New York, Richard R. Smith, 1931.
25. Conti PS, Lilien DL, Hawley K, et al: PET and [18F]-FDG in oncology: A clinical update. Nucl Med Biol 23:717-735, 1996.
26. Rigo P, Paulus P, Kaschten BJ, et al: Oncological applications of positron emission tomography with fluorine-18 fluorodeoxyglucose. Eur J Nucl Med 23:1641-1674, 1996.
27. Flanagan FL, Dehdashti F, Siegel BA, et al: Staging of esophageal cancer with FDG-PET. AmJ Roentgenol 168:417-424,1997.
28. Nolop KB, Rhodes CG, Brudin LH, et al: Glucose utilization in vivo by human pulmonary neoplasm. Cancer 60:2682-2689, 1987.
29. Dewan NA, Reed SD, Gupta NC, et al: FDG-PET imaging and transthoracic needle lung aspiration biopsy in evaluation of pulmonary lesions: A comparative risk-benefit analysis. Chest 108:441-446, 1995.
30. Lewis P, Griffin S, Marsden P, et al: Whole-body 18-F fluorodeoxyglucose positron emission tomography in preoperative evaluation of lung cancer. Lancet 344:1265-1266, 1994.
31. Bury T, Dowlati A, Paulus P, et al: Staging of non small cell lung cancer by whole-body 18-FDG-PET. Eur J Nucl Med 23:204-206, 1996.
32. Valk PE, Pounds TR, Hopkins DM: Staging of non small cell lung cancer by whole-body positron emission tomography. Ann Thorac Surg, 60:1573-1582,1995.
33. Cho ZH, Ro YM: Reduction of susceptibility artifact in gradient echo imaging. Magn Reson Med 23:193-200, 1992.
34. Bergin CJ, Glover GM, Pauly JM: Lung parenchyma: Magnetic susceptibility in MR imaging. Radiology 180: 845-848, 1991.
35. Bergin CJ, Noll DC, Pauly JM, et al: MR imaging of lung parenchyma: A solution to susceptibility. Radiology 183:673-676, 1992.
36. Gefter WB, Davis SD, Gurney JW, et al: Thoracic radiology: RSNA95 meeting notes. Radiology 198: 926-931, 1996.
37. Kneeland JB, Kellman GM, Middleton WD, et al: Diagnosis of diseases of the supraclavicular region by use of MR imaging. Am J Roentgenol 148:149-151, 1987.
38. Match RM: Radiation-induced brachial paralysis. Arch Surg 110:384-386, 1975.