Intracranial germ cell tumors at unusual locationsC Rana1, N Krishnani1, R Kumar2
1 Department of Pathology, Sanjay Gandhi Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
2 Department of Neurosurgery, Sanjay Gandhi Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0022-3859.105449
Source of Support: None, Conflict of Interest: None
Germ cell tumor (GCT) is relatively uncommon in intracranial locations. They constitute ~ 0.3-0.6% of intracranial neoplasms and encompass a wide pathologic range. The majority occurs in young adults and occupies the midline locations like pineal gland followed by suprasellar compartment. These tumors are rare in the cerebral hemisphere, basal ganglia, thalamus and ventricles. Neuroimaging studies cannot differentiate GCTs from other tumors, and therefore, the diagnosis usually requires histological confirmation. Germ cell tumors can be divided into major groups including germinomas and nongerminomatous GCTs (NGGCTs). Their proper identification as well as histopathological typing is important as treatment and prognosis vary greatly between different groups. Germinomas have a superior prognosis and are more radiosensitive as compared to non-germinomatous germ cell tumors. Standard management is still controversial. In this case series we are presenting three cases of intracranial germ cell tumors arising in two unusual locations, that is intraventricular and thalamic region. Apart from the clinical, radiological, histopathological and surgical details we also discuss the various aspects of intracranial germ cell tumors.
Keywords: Germ cell tumors, intracranial, intraventricular, thalamic
Intracranial germ cell tumors (GCTs) vary in their geographic incidence ranging 0.3% and 0.6% of all intracranial tumors and 3-4% of those affecting children.  GCTs of the central nervous system (CNS) are usually primary neoplasms of young with 90% afflicting younger than 20 years.
CNS variants of germ cell tumors also occupy the midline location similar to extragonadal germ cell tumors. Eighty percent or more arise in the pineal gland followed by the suprasellar compartment. Germ cell tumors of the CNS confined to the cerebral hemisphere, basal ganglia or thalami are very rare and those arising in ventricles are even rarer.  Primary CNS GCTs share histologic, genetic, and therapeutic similarities with extracranial GCTs. Radiological features do not reliably distinguish GCTs from other neoplasms making histopathological evaluation important for diagnosis. Adequate staging and deciphering the histology of CNS GCTs are important factors used to properly stratify patients into appropriate treatment groups. However, treatment of this neoplasm in intracranial location is still a controversial subject. In this case report we are describing three cases of germ cell tumors at unusual intracranial locations including intraventricular and thalamic regions.
We describe three cases of intracranial mixed germ cell tumor arising from two different and unusual locations. [Table 1] describes the clinical, radiological, surgical as well as histopathological details of these cases.
Case 2 was again admitted after three months with features of hydrocephalus and ascites. Radiologically there was hydrocephalus with dilatation of lateral and third ventricle along with presence of residual tumor. The ascites was hemorrhagic and the cytopathological examination showed presence of malignant cells. Craniospinal imaging was done which did not reveal metastatic deposits elsewhere. Finally, ventriculo-atrial shunting was done and the patient improved.
CNS GCTs represent a rare heterogeneous group of lesions that commonly arise from the pineal and/or suprasellar regions in patients of all ages. In the Western countries these neoplasms constitute 0.3-0.6% of primary intracranial tumors, and approximately 3-4% of those affecting children with the highest incidence reported in Japan (8-15%). 
Eighty to ninety percent cases are discovered in the first two decades of life with peak incidence between 10-14 years. The tumor predominates in the pineal region in boys but in the suprasellar region in girls and all the histological variants have a predilection for males. 
Similar to other extragonadal germ cell tumors, the intracranial GCTs also affect the midline with 80% of the cases arising in structures around the third ventricle with the pineal gland being the most common location followed by the suprasellar compartment. Thalamic, cerebral hemispheric, intrasellar and intramedullary variants are very rare and those arising in the ventricle are rarer. , Germinomas arising from the thalamus and basal ganglia account for 4-20% of all intracranial GCTs.  As a whole, intraventricular tumors make up 10% of tumors in the but germ cell tumors in intraventricular location are extremely rare as are the germ cell tumors of the thalamus.
Clinical presentation depends on the location, duration and histological type of the tumor. Intraventricular tumors obstruct the flow of the cerebrospinal fluid (CSF) leading to obstructive hydrocephalus resulting in pressure on the surrounding brain parenchyma. This was seen in Case 1 and Case 2 where the patients presented with features like headache, vomiting and blurring of vision. Diagnosis of basal ganglionic GCTs at an early stage can be difficult owing to the insidious onset of neurological deficits. The major signs and symptoms include progressive hemiparesis, cognitive decline and psychosis. These symptoms do not parallel with the size of the tumor and progress slowly in most cases. Acute deterioration is related with intra-tumoral bleeding.  Because of bleeding the cases would be misdiagnosed as vascular malformation preoperatively.
According to the World Health Organization (WHO) classification they are broadly classified as germinomatous, non-germinomatous and mixed germ cell tumor. NGCTs include teratoma, yolk sac tumor, embryonal and choriocarcinoma. Only germinoma and teratoma are likely to be encountered as pure tumor types.  They can also be classified according to the presence or absence of tumor markers. These secreted markers can be measured in both serum and CSF, though CSF levels are a more sensitive and reliable measure for diagnosis. The most common markers are alpha-fetoprotein (AFP) and β-human chorionic gonadotropin (β-HCG), but placental alkaline phosphatase and the soluble isoform of c-Kit may become clinically relevant in the future. , A new classification system was recently adopted in some European studies separating CNS GCTs into "secreting" or "non-secreting" tumors. Secreting tumors are defined as presenting with an elevated CSF AFP≥10 ng/ml or above the local laboratory's normal range and/or a CSF β-HCG level>50 IU/l or greater than the accepted laboratory normal range[Figure 1]. 
Radiographic characteristics of CNS GCTs are unable to reliably differentiate germinoma or NGGCTs from other tumors. Radiological features are very similar in all GCTs, therefore limiting their usefulness in determining the exact histology of these tumors. The main differential diagnosis is from malignant tumors such as glioma and lymphomas. Confirmation of the diagnosis requires measurement of serum and CSF tumor markers and/or biopsy. 
Accurate histological identification and subclassification is critical for treatment planning as well as predicting the prognosis. Best outcome is with pure localized germinoma (which is generally radiocurable and chemosensitive) as well as mature teratomas which can be completely resected. Spontaneous regression of germinoma has been noted in some studies.  Yolk sac tumor, embryonal carcinoma, choriocarcinomas and mixed germ cell tumors are often not amenable to surgery as well as adjuvant treatment and carry a high mortality too. 
Case 1 and 3 in our report had teratomatous and germinomatous component and in both these cases surgical removal could be done in toto. Case 3 received postoperative radiotherapy with significant improvement. Postoperative radiotherapy was also planned in Case 1 but unfortunately the patient died due to anterior cerebral artery infarction. Case 2 had a yolk sac tumor component in addition to teratomatous and germinomatous component. Complete surgical removal could not be done leaving a residual tumor. The patient returned later with hydrocephalus and ascites which showed presence of malignant cells.
In Western countries, with the advances of microsurgical techniques and lower surgical morbidity, the choice of surgery is an optimal option accompanied by radiotherapy. Chemotherapy has also been explored in an effort to reduce radiation therapy doses. Several studies have confirmed the feasibility of this approach while maintaining excellent survival rates, but the number of treated patients has been small.  In Japan where the incidence of CNS GCTs is highest the neoadjuvant chemo-radiotherapy is conducted without surgical biopsy of tumors as far as possible in order to prevent the frequently reported surgical dissemination of tumors. Management of intracranial GCTs is still controversial.