Relationship With Specific Systemic Cancers

In patients with an unknown primary site and brain metastases, the lung represents the most common primary tumor site discovered antemortem, accounting for between 45% and 83% of identifiable primary sites (see Table 60-2). The lung also appears to be the most common primary site regardless of whether it becomes known early (within 2 months) or late (after 2 months) after the diagnosis of brain metastases.33,46 In contrast, when the primary site is discovered only after autopsy, there does not appear to be a predominant organ of origin.14,26,30 In the general population of patients with brain metastases, the lung is identified as a primary site in 50% to 70% of patients and is followed in frequency by breast cancer metastases in women.24,34,49 By comparison, the breast appears to be under-represented as a primary tumor site in patients in whom the site initially remains occult at diagnosis or autopsy14,26,28,30,33,42; in these studies, the abdominal and pelvic organs are typically the second most common primary site. This difference may be a result of the earlier diagnosis of primary breast cancer, which tends to metastasize at an advanced stage of the disease. Other primary tumor sites that become manifest include the skin and upper aerodigestive tract (e.g., melanoma, squamous cell carcinoma, adenocarcinoma), thyroid gland, hematologic system, and reproductive organs.

The high incidence of the lung as the primary site is not surprising given the high incidence of lung cancer in general, ease of detection of lung masses, and direct vascular connection between the lungs and brain that permits a convenient route for hematogenous dissemination. However, it is also possible that a lung mass may actually represent metastatic disease from another organ rather than a primary lung tumor, because most organs producing tumors that metastasize to the brain do so by first sending metastases to the lungs.40,45 Therefore finding a lung mass on a chest x-ray should be interpreted cautiously.

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