Apart from the above, most carcinomas reach the brain by hematogenous spread. Almost one-third of metastases to the brain originate in the lung and half this number in the breast; melanoma is the third most frequent source in most series, and the gastrointestinal tract (particularly the colon and rectum) and kidney are the next most common, in part reflecting the prevalence of each of these tumors but also because of a tropism for the nervous system, as noted below. Carcinomas of the gallbladder, liver, thyroid, testicle, uterus, ovary, pancreas, etc., account for the remainder. Tumors originating in the prostate, esophagus, oropharynx, and skin (except for melanoma) only rarely metastasize to the substance of the brain. From a different perspective, certain neoplasms are particularly prone to metastasize to the brain—75 percent of melanomas do so, 55 percent of testicular tumors, and 35 percent of bronchial carcinomas, of which 40 percent are small cell tumors according to Posner and Chernik. They describe a solitary metastasis in 47 percent of cases, a somewhat higher figure than that observed in our practice and reported by others (see Henson and Urich). The metastatic tumors most likely to be single come from kidney, breast, thyroid, and adenocarcinoma of the lung. Small cell carcinomas and melanomas more often tend to be multiple, but exceptions abound. All of these comments relating to the proportion of metastases from various origins and the propensity for a given tumor to metastasize to the brain are similar to more recent surveys.
Generally, the cerebral metastasis forms a circumscribed mass, usually solid but sometimes in the form of a ring (i.e., cystic), that excites little glial reaction but much regional vasogenic edema. Edema alone is often evident on imaging studies until the administration of contrast exposes small tumor nodules (Fig. 30-10). Metastases from melanoma and chorioepithelioma are often hemorrhagic, but it is not unusual for tumors originating in lung, thyroid, and kidney to exhibit this characteristic. In a number of these cases, one-quarter in some series, the first manifestation of the metastasis is an intratumoral hemorrhage. The relative frequency of lung cancer makes it the most common metastatic tumor to bleed, even though only a small proportion does so.
The usual clinical picture of metastatic carcinoma of the brain is of seizures, headache, focal weakness, mental and behavioral abnormalities, ataxia, aphasia, or signs of increased intracranial pressure—all inexorably progressive over a few weeks or months. In addition, a number of unusual syndromes may occur. One that presents particular difficulty in diagnosis is a diffuse cerebral disturbance with headache, nervousness, depressed mood, trembling, confusion, and forgetfulness, resembling a relatively rapid dementia from degenerative disease. Cerebellar metastasis, with headache, dizziness, and ataxia (the latter being brought out only by having the patient walk) is another condition that may be difficult to diagnose. Brainstem metastases, most often originating in the lung, are rare but distinctive, giving rise to diplopia, imbalance, and facial palsy, as in the characteristic case described by Weiss and Richardson.
The onset of symptoms from brain metastases may occasionally be abrupt or even “stroke-like” rather than insidious. Some cases of sudden onset can be explained by bleeding into the tumor and others perhaps by tumor embolism that occludes a cerebral vessel. In most cases, the explanation for this temporal profile is not known. Also, non-bacterial thrombotic (marantic) endocarditis with cerebral embolism must be suspected when a stroke-like event occurs in a cancer patient. It is not unusual for one or other of these neurologic manifestations to precede the discovery of a pancreatic, bowel, gastric, breast, or lung carcinoma.