Cerebral metastases as first symptom of cancer: a clinico-pathologic study

Symptomatic brain metastases of carcinomas in patients without a previously diagnosed malignancy are frequent in neurosurgical series. Such tumors often lack distinctive morphological characteristics so that the routine histological examination can be unsuccessful in identifying the site of origin. Objectives of the present study were to evaluate the frequency of brain metastases as the only manifestation of an unknown primary cancer by the retrospective analysis of a series of consecutively operated single cerebral metastases; to verify the efficacy of clinical investigations in detecting the site of origin; to investigate whether the primary site can be identified by the immunohistochemical study of the neurosurgical specimens. Antibodies to the following antigens were used: carcinoembryonic antigen (CEA), carbohydrate antigen (CA)19.9, CA125, BCA-225, cytokeratin 20, PSA, HMB-45. Out of 181 patients operated for single cerebral metastasis of carcinoma, 99 (54.7%) were in patients without any previously diagnosed systemic neoplasm. In 26.7% the primary remained undiagnosed after clinical investigations, in 9 cases even at autopsy. PSA and HMB45 antibodies specifically identified metastases from prostate carcinomas and skin melanomas, respectively. No other specific immunophenotype was identified; the immunoreactivity of the single cases was more or less suggestive for a primary site. Precocious metastases of lung carcinomas expressed CEA more frequently than late metastases. It has been hypothesized that CEA plays some role as a contact mediating device. CEA expression can have some link with the tendency to metastasize precociously to the brain. No major difference of p53 and k-ras expression has been found in precocious versus late brain metastases.