pineal_germinoma_serum_and_cerebrospinal_fluid_biomarkers

Pineal germinoma serum and cerebrospinal fluid biomarkers

see Germ cell tumor biomarkers

Choriocarcinomas and germinomas are associated with elevated β-hCG 1) 2) 3) 4) 5) 6) 7) 8) 9) 10) 11) 12); nevertheless, β-hCG levels in germinomas are inconsistent, and germinomas with elevated β-hCG may have a poor prognosis 13) 14)15) 16).

Germinomas are also associated with elevated lactate dehydrogenase and placental alkaline phosphatase 17) 18) 19).

Germ cell tumors in the brain release hormones directly into the CSF. Comparing CSF and serum β-hCG levels is a particularly important step in the workup of a pineal tumor, as patients with metastatic disease do not benefit from resection of the primary tumor. Accordingly, an important workup step before obtaining CSF is a systemic assessment; if the systemic assessment reveals a primary site, CSF sampling is not necessary 20).

In a review, Carr et al. searched PubMed using the following keywords: biomarkers, germ cell tumors, germinoma, melatonin, pineal, pineal gland, pineal neoplasm, pinealoma, pineal parenchymal cell tumor, pineal region, and pineal tumor.

They limited the search to full-text English articles and identified other relevant sources from the reference lists of identified articles.

Serum and CSF biomarker assays have a role in cases of suspected pineal germ cell tumor or parenchymal neoplasms. Biomarkers including alpha-fetoprotein, beta human chorionic gonadotropin, and placental alkaline phosphatase inform diagnosis and treatment and are important for monitoring germ cell tumor response to treatment. No biomarkers are currently available that inform the diagnosis or treatment of pineal parenchymal tumors, although melatonin assays may have a role in monitoring response to treatment.

Serum and CSF biomarkers in conjunction with clinical and radiographic evidence of a pineal region tumor can inform the decision whether to undertake stereotactic biopsy or surgical excision or whether to proceed straight to medical treatment 21).

Germ cell tumors may secrete measurable oncoproteins such as Beta human chorionic gonadotropin (HCG) and Alpha fetoprotein in the serum or CSF. Pure germinomas, by definition, only secrete HCG. The α-fetoprotein levels in the serum and CSF are normal.

1)
Yamamoto I, Kageyama N. Microsurgical anatomy of the pineal region. J Neurosurg. 1980. August;53(2):205-221. doi: 10.3171/jns.1980.53.2.0205.
2) , 17)
Bruce JN, Connolly ES, Sonabend AM. Pineal cell and germ cell tumors. In: Kaye AH, Laws ER, eds. Brain Tumors. 3rd ed. New York, NY: Elsevier Limited; 2012.
3)
Allen JC, Nisselbaum J, Epstein F, Rosen G, Schwartz MK. Alphafetoprotein and human chorionic gonadotropin determination in cerebrospinal fluid. An aid to the diagnosis and management of intracranial germ-cell tumors. J Neurosurg. 1979. September;51(3):368-374.
4)
Haase J, Børgaard-Pedersen B.. Alpha-feto-protein (AFP) and human chorionic gonadotropin (HCG) as biochemical markers of intracranial germ-cell tumours. Acta Neurochir (Wien). 1979;50(1-2):67-69. doi: 10.1007/BF01813551.
5)
Neuwelt EA, Smith RG. Presence of lymphocyte membrane surface markers on “small cells” in a pineal germinoma. Ann Neurol. 1979. August;6(2):133-136. doi: 10.1002/ana.410060211.
6)
Wilson ER, Takei Y, Bikoff WT, O'Brien MS, Tindall GT, Boehm WM. Abdominal metastases of primary intracranial yolk sac tumors through ventriculoperitoneal shunts: report of three cases. Neurosurgery. 1979. September;5(3):356-364.
7)
Arita N, Ushio Y, Hayakawa T, et al. . Serum levels of alpha-fetoprotein, human chorionic gonadotropin and carcinoembryonic antigen in patients with primary intracranial germ cell tumors. Oncodev Biol Med. 1980;1(4-5):235-240.
8)
Jooma R, Kendall BE. Diagnosis and management of pineal tumors. J Neurosurg. 1983. May;58(5):654-665. doi: 10.3171/jns.1983.58.5.0654.
9)
Bamberg M, Metz K, Alberti W, Heckemann R, Schulz U. Endodermal sinus tumor of the pineal region. Metastases through a ventriculoperitoneal shunt. Cancer. 1984. Sep 1;54(5):903-906.
10)
Jennings MT, Gelman R, Hochberg F. Intracranial germ-cell tumors: natural history and pathogenesis. J Neurosurg. 1985. August;63(2):155-167.
11)
Page R, Doshi B, Sharr MM. Primary intracranial choriocarcinoma. J Neurol Neurosurg Psychiatry. 1986. January;49(1):93-95.
12)
Russel DS, Rubinstein LJ. Tumors and tumor like lesions of maldevelopmental origin. Pathology of Tumors of the Nervous System. 5th ed London, England; Edward Arnold: 1989;693-695.
13)
Uematsu Y, Tsuura Y, Miyamoto K, Itakura T, Hayashi S, Komai N. The recurrence of primary intracranial germinomas. J Neuro-Oncol. 1992. July;13(3):247-256. doi: 10.1007/BF00172477.
14)
Yoshida J, Sugita K, Kobayashi T, et al. . Prognosis of intracranial germ cell tumours: effectiveness of chemotherapy with cisplatin and etoposide (CDDP and VP-16). Acta Neurochir (Wien). 1993;120(3-4):111-117.
15)
Utsuki S, Kawano N, Oka H, Tanaka T, Suwa T, Fujii K. Cerebral germinoma with syncytiotrophoblastic giant cells: feasibility of predicting prognosis using the serum hCG level. Acta Neurochir (Wien). 1999;141(9):975-977. doi: 10.1007/s007010050404.
16)
Utsuki S, Oka H, Tanaka S, Tanizaki Y, Fujii K. Long-term outcome of intracranial germinoma with hCG elevation in cerebrospinal fluid but not in serum. Acta Neurochir (Wien). 2002. November;144(11):1151-1154; discussion 1154-1155. doi: 10.1007/s00701-002-1008-4.
18)
Metcalfe S, Sikora K. A new marker for testicular cancer. Br J Cancer. 1985. July;52(1):127-129.
19)
Shinoda J, Miwa Y, Sakai N, et al. . Immunohistochemical study of placental alkaline phosphatase in primary intracranial germ-cell tumours. J Neurosurg. 1985. November;63(5):733-739.
20) , 21)
Carr C, O'Neill BE, Hochhalter CB, Strong MJ, Ware ML. Biomarkers of Pineal Region Tumors: A Review. Ochsner J. 2019 Spring;19(1):26-31. doi: 10.31486/toj.18.0110. Review. PubMed PMID: 30983898; PubMed Central PMCID: PMC6447205.
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