Central Nervous System Germinoma Workup

Updated: May 04, 2015
  • Author: Amani A Al Kofide, MD; Chief Editor: Jules E Harris, MD, FACP, FRCPC  more...
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Laboratory Studies

Studies to detect the hormonal dysfunction that may occur in patients with central nervous system (CNS) germinomas are as follows:

  • Diabetes insipidus – Serum sodium, serum osmolality, and urine osmolality
  • Hypopituitarism – Thyroid function tests, growth hormone levels, cortisol levels
  • Gonadal dysfunction – Testosterone level in males; prolactin level in females

Tumor markers may be measured in serum and cerebrospinal fluid (CSF). [49, 50] Tumor marker levels are usually higher in CSF than in serum. [49] Detection of elevated tumor markers may be sufficient for diagnosis in patients in whom endoscopic biopsy is not considered possible.

Alpha-fetoprotein (AFP) levels may be elevated in pure endodermal sinus tumor (yolk sac), embryonal carcinoma, and malignant teratoma. However, AFP levels may be normally elevated both in serum and CSF of neonates and infants. Accurate interpretation of the AFP level must take into account the normal variation seen in this age group. In normal infants, the median AFP levels in CSF are as follows:

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

Other relevant tumor marker findings are as follows:

  • Levels of beta human chorionic gonadotropin (β-hCG) above 50-100 IU/L indicate the presence of choriocarcinoma while lower levels may indicate pure germinoma that contain syncytotrophoblastic giant cells. [17, 51, 32, 6]
  • Carcinoembryonic antigen (CEA) levels may be increased in nongerminomatous germ cell tumors (NGGCTs) or their components.

In addition to tumor marker measurement, CSF cytology may be performed to detect malignant cells. [52]


Imaging Studies

CT scan of the brain

Findings are as follows:

  • Germinomas show a homogeneous pattern and are hyperdense compared with brain tissue; with pineal gland tumors, calcification of the gland may be seen
  • NGGCTs are irregular in shape, with edema, and are less dense than germinomas
  • Mature teratomas have mixed densities, with large cysts and areas of calcification with distinct tumor margins

Magnetic resonance imaging

Findings are as follows:

  • MRI of the brain and spine with and without gadolinium is the gold standard imaging study
  • Leptomeningeal metastasis is present at diagnosis in 10-15% of patients [5]
  • See images below
    MRI of the brain - T1 weighted-image- coronal view MRI of the brain - T1 weighted-image- coronal view- showing a heterogeneously enhancing, multicystic mass in the suprasellar region
    MRI of the brain - axial view- heterogeneous mass MRI of the brain - axial view- heterogeneous mass lesion measuring approximately 3.2 x 2.9 x 4.0 cm.
    MRI of the brain - T1-weighted image - post-gadoli MRI of the brain - T1-weighted image - post-gadolinium sagittal view- A suprasellar lesion that severely compresses the optic chiasm encases the posterior aspect of the optic nerves bilaterally and causes superior displacement of the third ventricle, with significant compression of the brain stem.
  • Germinomas are homogeneous and show isointensity or slightly low signal intensity on T1-weighted images, and isointensity or high intensity on T2-weighted images
  • NGGCTs are more heterogeneous and may have hemorrhage
  • Malignant teratomas are heterogeneous, with small cysts and irregular tumor margins, and may demonstrate peri-tumor edema
  • MRI is excellent in delineating tumor anatomy and may suggest specific tumor type; however, the findings may be similar for germinomas, NGGCTs, and pineal parenchymal tumors. Therefore, imaging studies alone may not suffice for precise diagnosis.

Positron emission tomography

Several studies have investigated the utility of positron emission tomography (PET) scans. In a retrospective review of 10 patients, Okochi et al reported that 18F-fluorodeoxyglucose PET(FDG-PET) was able to detect the presence of germinomas while 11C-methionine PET (MET-PET) can help define tumor contour to plan for biopsy or surgery. [53] Limited information is available on the value of 18F-fluroethylcholine PET/MRI for the diagnosis of intracranial GCTs and followup by assessing for residual tumor. [54]


Histologic Findings

The World Health Classification (WHO) system of CNS GCTs is based on histology, serum and CSF tumor markers, and protein markers on tumor cells. [17, 6] See Table 1, below.

Table 1: Immunohistochemical findings of CNS GCTs [6, 17, 31] (Open Table in a new window)

Tumor type β- HCG AFP PLAP c-Kit
Germinoma-Pure - - +/- +
Germinoma with STGC + - +/- +
Endodermal sinus tumor - + +/- -
Choriocarcinoma + - +/- -
Embryonal Carcinoma - - + -
Mixed Teratoma +/- +/- +/- +/-
Mature Teratoma - - - -
Immature teratoma +/- +/- - +/-


Histological findings are as follows:

  • Germinoma is composed of undifferentiated, uniform large cells with abundant glycogen-rich cytoplasm arranged in nests separated by bands of connective tissue along trophoblastic lines. Scattered β-hCG–secreting syncytiotrophoblasts may be present.
    Biopsy specimen from an intracranial germ cell tum Biopsy specimen from an intracranial germ cell tumor - Large tumor cells with large nuclei; prominent nucleoli; and abundant, clear cytoplasm (rich in glycogen) are noted among reactive inflammatory cells--lymphocytes and histiocytes. Elsewhere there are well-formed granulomas, a well-known phenomenon in germinomas, especially of the pineal region.
  • Embryonal carcinoma is composed of large cells with a high mitotic index that proliferate in cohesive nests and sheets demonstrating zones of coagulative necrosis.
  • Choriocarcinoma is characterized by extraembryonic differentiation along trophoblastic lines with βHCG-secreting syncytiotrophoblasts.
  • Endodermal sinus tumors are composed of primitive-appearing epithelial cells linked to extraembryonic mesoblast.
  • Mixed germ cell tumors have more than one histological component.


Histological findings in teratomas are as follows:

  • Mature teratomas comprise fully differentiated tissue elements of ectoderm, mesoderm, and endoderm.
  • Immature teratomas contain incompletely differentiated tissue elements.
  • Teratomas with malignant transformation usually contain rhabdomyosarcoma or undifferentiated sarcoma.


The diagnostic work-up for CNS GCTs should include MRI of the brain and spine, measurement of the tumor markers β -hCG and AFP in both serum and CSF, and tissue confirmation by biopsy. [49, 50, 55]

  • MRI of the brain and spine are essential for diagnosis, assessing extent of intracranial disease and detecting metastatic disease
  • Postoperative MRI of the brain is essential to assess residual tumor
  • CSF cytology is used to detect malignant cells [52]
  • Measurement of serum and CSF tumor markers including AFP and β-hCG. [49, 50]
  • Evaluation of the disease outside the CNS is usually unnecessary


Currently the recommendation for all patients with pineal and suprasellar tumors is to undergo surgical biopsy for histological confirmation, which is accomplished by means of endoscopic/stereotactic biopsy or open biopsy. Advances in endoscopic techniques have led to less morbidity and mortality with this procedure. Suprasellar tumors are generally more accessible to surgical biopsy than are pineal tumors.

Adequate specimen size is important because in NGGCT, a specimen that is too small may miss a tumor component and thus may not be representative of the actual tumor type.

Only patients with elevated serum or CSF levels of AFP or β-hCG >50-100 IU/ml do not warrant surgery for the sole purpose of tissue diagnosis [24, 51, 32] Diagnosis without tissue verification should be considered in such patients because high postoperative mortality has been reported after resection of secreting tumors.