Clinical Information

Alpha-fetoprotein (AFP) is an oncofetal glycoprotein, homologous with albumin, that is produced in early fetal life and in tumors arising from midline embryonic structures. AFP is synthesized in the yolk sac, liver, and gastrointestinal track of the fetus. In adults, the liver synthesizes AFP. AFP is not normally expressed in the central nervous system (CNS). AFP concentrations are increased in hepatomas and hepatocellular and colon carcinomas, as well as in germ-cell tumors arising from the ovaries and nonseminomatous germ-cell tumors of the testes and testicular teratocarcinomas.

Based on histologic components and differentiation, CNS germ cell tumors (GCT) are classified as either germinomatous or nongerminomatous germ cell tumors (NGGCT). NGGCT include embryonal carcinomas, yolk sac tumors, choriocarcinomas, and mixed tumors. Teratomas (including teratomas of testicular origin) are sometimes considered to be NGGCT. Germinomas comprise two-thirds of the CNS GCT, whereas NGGCT account for the other third. However, CNS GCT are rare, comprising only 1% to 2% of all primary CNS neoplasms. The presence of germinomas in the CNS, CNS involvement in metastatic cancer, and meningeal carcinomatosis may result in increased concentrations of AFP (and/or beta–human chorionic gonadotropin [hCG]) in cerebrospinal fluid (CSF). In some patients with primary or metastatic intracranial or intraspinal tumors containing trophoblasts, AFP secreted by trophoblasts can diffuse into the CSF. Following treatment, AFP elevation in CSF is a potential marker of tumor recurrence.

Increased concentrations of AFP in CSF are more indicative of sac tumors/yolk sac components in mixed GCT. High concentrations of hCG in CSF support the presence of choriocarcinomas/choriocarcinomatous components in mixed GCT. If a germ cell tumor is suspected, the measurement of CSF and serum AFP and hCG may be considered. The secretion of these tumor markers in the CSF is pathognomonic for NGGCT.