eMedicine Specialties > Oncology > Carcinomas of the Central and Peripheral Nervous System

Germinoma, Central Nervous System: Differential Diagnoses & Workup

Author: Amani AlKofide, MBBS, Assistant Professor, Alfaisal University College of Medicine; Consultant, Department of Pediatric Hematology and Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh
Contributor Information and Disclosures

Updated: Sep 2, 2009

Differential Diagnoses

Colloid Cysts
Craniopharyngiomas
Cysticercosis
Metastatic Cancer, Unknown Primary Site
Pineal Tumors
Pituitary Macroadenomas

Other Problems to Be Considered

Glial Tumors - astrocytomas, gangliomas
Granular cell tumor
Hamartomas
Meningiomas
Xanthogranuloma

Workup

Laboratory Studies

  • Studies to detect hormonal dysfunction
    • Diabetes insipidus – measure 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 - in serum and CSF24,25
    • Alpha-fetoprotein (AFP) may be normally elevated both in serum and CSF of neonates and infants. It has a wide variation. It reachs adult levels at the age of 8-12 months. Therefore accurate interpatation of rasied AFP must take into account the normal varation seen in this age group. In normal infants AFP in CSF is: median 61kIU/L in infants less than 31 days; median 1.2kIU/L in infants 32-110 days
    • AFP may be elevated in pure endodermal sinus tumor (yolk sac), embryonal carcinoma, and malignant teratoma.
    • β-hCG levels above 50-100 IU/L indicate the presence of choriocarcinoma while lower levels may indicate pure germinoma that contain syncytotrophoblastic giant cells12,39,53 .
    • Carcinoembryonic antigen (CEA) levels may be increased in NGGCTs or their components.
    • CSF tumor marker levels are usually higher than serum levels.24
    • Detection of elevated tumor markers may be sufficient for diagnosis in patients in whom endoscopic biopsy is not considered possible.
  • CSF cytology – to detect malignant cells.26

Imaging Studies

  • CT scan of the brain
    • 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 
    • MRI of the brain and spine with and without gadolinium is the gold standard radiological imaging study. See images below.

      • MRI of the brain - T1 weighted-image- coronal vie...

        MRI of the brain - T1 weighted-image- coronal view- showing a heterogeneously enhancing, multicystic mass in the suprasellar region

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        MRI of the brain - T1 weighted-image- coronal vie...

        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.

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        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-gadol...

        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.

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        MRI of the brain - T1-weighted image - post-gadol...

        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.

Procedures

  • Histological confirmation 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.
  • 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.
  • Suprasellar tumors are generally more accessible to surgical biopsy than are pineal tumors.
  • Currently the recommendation for all patients with pineal and suprasellar tumors is to undergo surgical biopsy for histological confirmation.
  • 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 diagnosis15,39,53 Diagnosis without tissue verification should be considered in such patients because high postoperative mortality has been reported after resection of secreting tumors.

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.6,12

  • 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 tu...

      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.

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      Biopsy specimen from an intracranial germ cell tu...

      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.
  • Teratoma
    • 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.
Table: Immunohistochemical findings of CNS GCTs6,12,21  

Tumor type  Finding
  AFP β-HCG PLAP  c-kit
Germinoma
Pure - - ++ +
With STGC - +  ++ +

Teratoma +/- -  - -

Yolk sac tumor ++ - -/+ -

Embryonal carcinoma +/- -/+ +/- -

Choriocarcinoma - ++ +/- -

PLAP=placental-like alkaline phosphatase
STGC=syncytiotrophoblasts

Staging

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.24 25,27 .

  • 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 cells26
  •  Measurement of serum and CSF tumor markers including AFP and β-hCG.24,25
  • Evaluation of the disease outside the CNS is usually unnecessary

More on Germinoma, Central Nervous System

Overview: Germinoma, Central Nervous System
Differential Diagnoses & Workup: Germinoma, Central Nervous System
Treatment & Medication: Germinoma, Central Nervous System
Follow-up: Germinoma, Central Nervous System
Multimedia: Germinoma, Central Nervous System
References
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References

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Further Reading

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Keywords

Intracranial germ cell tumors, germinoma, nongerminomatous germ cell tumor, germ cell tumor, teratoma, pineal lesions, suprasellar lesions, gonadotrophines, tumor markers, alpha-fetoprotein (AFP),  beta-human chorionic gonadotrophins (β-hCG) , primordial germ cells, Klinefelter syndrome, syncytiotrophoblasts
 
 

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Contributor Information and Disclosures

Author

Amani AlKofide, MBBS, Assistant Professor, Alfaisal University College of Medicine; Consultant, Department of Pediatric Hematology and Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh
Amani AlKofide, MBBS is a member of the following medical societies: American Society of Pediatric Hematology/Oncology
Disclosure: Nothing to disclose.

Medical Editor

Lodovico Balducci, MD, Professor of Oncology and Medicine, University of South Florida College of Medicine; Division Chief, Senior Adult Oncology Program, H Lee Moffitt Cancer Center and Research Institute
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Benjamin Movsas, MD, Vice-Chairman, Department of Radiation Oncology, Fox Chase Cancer Center
Benjamin Movsas, MD is a member of the following medical societies: American College of Radiology, American Radium Society, and American Society for Therapeutic Radiology and Oncology
Disclosure: Nothing to disclose.

CME Editor

Rajalaxmi McKenna, MD, FACP, Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Jules E Harris, MD, Clinical Professor of Medicine, Division of Hematology/Medical Oncology, Department of Internal Medicine, University of Arizona College of Medicine at Tucson; Consulting Staff, Arizona Cancer Center
Jules E Harris, MD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Immunologists, American Society of Hematology, and Central Society for Clinical Research
Disclosure: GlobeImmune Salary Consulting; Amplimed Consulting fee Consulting; FibroGen Consulting fee Consulting

 
 
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