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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Simrat Sarai, M.D. [2]

Overview

An elevated concentration of AFP and beta-hCG in the serum and CSF, and CSF cytology to detect malignant cells is diagnostic of intracranial germ cell tumors. In patients in whom endoscopic biopsy is not considered possible, detection of elevated tumor markers may be sufficient for diagnosis.

Laboratory Findings

The following tests are done for intracranial germ cell tumors:

  • CSF cytology to detect malignant cells
  • Measurement of AFP and beta-hCG in the CSF and serum
    • Tumor marker levels are usually higher in CSF than in serum. In patients in whom endoscopic biopsy is not considered possible, detection of elevated tumor markers may be sufficient for diagnosis.
    • Measurement of beta-hCG and AFP in the CSF is more sensitive than serum levels in detecting abnormalities. However, due to discordant serum and CSF tumor marker results that were observed, both serum and CSF tumor markers should be obtained in the absence of clinical contraindications. Lumbar CSF is considered more accurate for tumor markers and cytology than ventricular CSF.
    • Tumor markers from ventricular CSF can be used, if a lumbar puncture is contraindicated.[1][2]

Although elevated alpha-fetoprotein levels may be seen in the germ cell tumors; however, AFP levels may be normally elevated both in serum and CSF of neonates and infants. Alpha-fetoprotein (AFP) levels may be elevated in the following tumors:

Interpretation of the AFP level must take into account the normal variation seen in this age group. The median AFP levels in CSF, in normal infants, are as follows:

Age AFP levels
≤31 days
  • 61 kIU/L
32-110 days
  • 1.2 kIU/L
8-12 months
  • Adult levels

Usually, pure germinomas and mature teratomas present with normal levels of AFP and beta-hCG in both serum and CSF. However, some histologically confirmed germinomas have elevated beta-hCG levels that are presumed to be due to beta-hCG secreting syncytiotrophoblasts. In beta-hCG secreting syncytiotrophoblasts, elevations of serum beta-hCG are generally limited (<50 IU/L), although some tumors have levels >100 IU/L.[3][4][5][6][7] The relevant tumor marker findings is shown below in a tabular form:

Tumor marker Features
beta human chorionic gonadotropin (β-hCG)
  • Levels of beta human chorionic gonadotropin (β-hCG) above 50-100 IU/L indicate the presence of choriocarcinoma
  • Lower levels of β-hCG may indicate pure germinoma that contain syncytiotrophoblastic giant cells
  • Pure endodermal sinus tumor or pure choriocarcinomas are often associated with dramatic elevations beta-hCG (>1000 IU/L), whereas immature teratomas have less dramatic elevations of beta-hCG.
Carcinoembryonic antigen (CEA)
  • Carcinoembryonic antigen (CEA) levels may be increased in nongerminomatous germ cell tumors (NGGCTs) or their components.
Alpha fetoprotein (AFP)
  • Any tumor with an elevated AFP (>10 microg/L) can be assumed to contain elements of endodermal sinus tumor and/or immature teratoma
  • Pure endodermal sinus tumor or pure choriocarcinomas are often associated with dramatic elevations in AFP (>500 microg/L), whereas immature teratomas have less dramatic elevations of AFP.
  • A serum AFP >1000 microg/L has been identified as a poor prognostic indicator, but since a significant proportion of these tumors have mixed components, it is not advisable to use tumor markers for risk stratification without a tissue diagnosis

References

  1. Kim A, Ji L, Balmaceda C, Diez B, Kellie SJ, Dunkel IJ; et al. (2008). "The prognostic value of tumor markers in newly diagnosed patients with primary central nervous system germ cell tumors". Pediatr Blood Cancer. 51 (6): 768–73. doi:10.1002/pbc.21741. PMID 18802946.
  2. Horowitz MB, Hall WA (1991). "Central nervous system germinomas. A review". Arch Neurol. 48 (6): 652–7. PMID 2039390.
  3. Goodwin TL, Sainani K, Fisher PG (2009). "Incidence patterns of central nervous system germ cell tumors: a SEER Study". J Pediatr Hematol Oncol. 31 (8): 541–4. doi:10.1097/MPH.0b013e3181983af5. PMID 19636276.
  4. Sato K, Takeuchi H, Kubota T (2009). "Pathology of intracranial germ cell tumors". Prog Neurol Surg. 23: 59–75. doi:10.1159/000210053. PMID 19329861.
  5. Kleihues, P, and W. K. Cavenee. Pathology and genetics of tumours of the nervous system. Lyon: IARC Press, 2000. Print.
  6. Shibamoto Y (2009). "Management of central nervous system germinoma: proposal for a modern strategy". Prog Neurol Surg. 23: 119–29. doi:10.1159/000210058. PMID 19329866.
  7. Shibamoto Y, Oda Y, Yamashita J, Takahashi M, Kikuchi H, Abe M (1994). "The role of cerebrospinal fluid cytology in radiotherapy planning for intracranial germinoma". Int J Radiat Oncol Biol Phys. 29 (5): 1089–94. PMID 8083078.


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