Germinoma (intracranial germinoma, dysgerminoma, extra-gonadal seminoma) is a germ cell neoplasm of the brain.
Although the term “germinoma” may be used for the tumors of the ovaries, testis and the mediastinum (thymus), usually it refers to a brain tumor.
Therefore, germinoma is a tumor of the central nervous system which originates from the germ cells. Usually the tumor develops on the midline of the brain, in the majority of cases – in the pineal gland or in the suprasellar region. Germinomas comprise about 40-50% of all pineal neoplasms and the most of the intracranial germ cell tumors. The symptoms of germinoma are caused by an increased intracranial pressure and compression of the nearby brain structures.
The peak incidence of germinoma is 10-12 years, about 90% of affected persons are younger than 20 when the diagnosis is made. Males are more likely to develop this tumor (male to female ratio of 5-22:1). However, suprasellar germinomas are more common for females.
Related: Ovarian dysgerminoma
Causes and risk factors
It is unknown exactly what is the reason of germinoma development. Germinomas arise from primordial germ cells during the embryonal phase. Some studies suggest that growth factor beta 1 may cause the migration of primordial germ cells.
Other studies reported the possible origin of germinoma cells from the pluripotent stem cells caused by the expression of germ cell–specific proteins – MAGE-A4, NY-ESO-1, and TSPY. Mutation of the c-KIT gene may be detected in germinomas.
Chromosomal imbalance such as gains of 1p, 8p, and 12q and losses of 13q and 18q may be seen in germinoma. Persons with Klinefelter syndrome, Down syndrome and type 1 neurofibromatosis are prone to develop intracranial germinomas.
Primary pineal tumors cause the rise of the intracranial pressure due to compression of the tectum and occlusion of the Sylvian aqueduct. This results in hydrocephalus and manifests with headaches, nausea and vomiting. Later ataxia, seizures and somnolence may occur.
In up to 50% of cases, compression of the tectum leads also to the development of the Parinaud syndrome. The syndrome is characterized by the nystagmus (rapid involuntary eye movements), upward gaze paralysis/paresis, failure of convergence and accommodation.
If the suprasellar region is involved hypopituitarism may occur, although this process may take up to several years. Diabetes insipidus, growth failure, delayed or precocious puberty and hypothyroidism may be seen as well.
The diagnosis of brain requires MRI/CT of the brain, although the exact type of the tumor may be identified only with the help of biopsy (endoscopic/stereotactic biopsy or open biopsy is performed usually).
Germinomas appear as soft grayish pink tumors with focal hemorrhages or small cysts. Microscopically, the tumor consists of large germ cells and small T-lymphocytes. The large cells have glycogen-rich cytoplasm and round vesicular nuclei. Some lesions are fibrotic. Germinomas stain positive for placental alkaline phosphatase, they may show variable staining for cytokeratins, the epithelial membrane antigen or vimentin.
Germinomas produce α-fetoprotein and β-human chorionic gonadotropin, these substances may be used as oncomarkers and identified in the serum and cerebrospinal fluid (CSF) to verify the diagnosis.
Hormone tests are required to detect the disbalance of endocrine system.
In majority of cases germinomas may be treated with radiotherapy alone or a combination of radiotherapy and chemotherapy.
Germinomas are highly sensitive to radiation therapy, and such treatment is usually enough to control the tumor. Chemotherapeutic agents seem to shrink the tumor effectively.
If possible a total resection of germinoma is done. The pineal area may be reached via several different surgical approaches:
- through the dilated lateral ventricle;
- through the posterior corpus callosum;
- under the occipital lobe;
- through the posterior fossa over the cerebellum.
Cisplatin, etoposide, vinblastine, bleomycin, carboplatin. ifosfamide and cyclophosphamide may be used in the treatment of the germinoma.
Vasopressin analogs (desmopressin acetate) are required to treat diabetes insipidus.
Five-year survival rate was estimated at 90%.