Pineal Germinoma

Nandakumar Srinivasan, MD; Aneesh Pakala, MD; Chandana Mukkamalla, MD; Alok Oswal, MD

Disclosures

South Med J. 2010;103(10):1031-1037. 

In This Article

Diagnosis

Prior to the advances in neurosurgery, the diagnosis of pineal germinoma was made presumptively on the basis of radiological features, the age and sex of the patient, and the response to a trial of empiric radiotherapy.[20] CT has been the mainstay of radiographic evaluation of pineal region tumors. CT demonstrates pineal germinoma as a high-density lesion with homogenous enhancement, clear or obscure margins, frequent calcification, and, in rare cases, with surrounding peritumoral edema.[21] MRI is the most reliable imaging study for CNS GCT. The solid portions of GCTs are isointense or hypointense on T1-weighted images and isointense or hyperintense on T2-weighted images with homogenous enhancement in gadolinium-diethylenetriamine penta-acetic acid (GD-DTPA) contrast studies.[21,22] Even with advances in the field of neuroimaging, it is considered very difficult to distinguish between pineal germinomas and gliomas or metastases on the basis of imaging alone.[20]

Clinicians currently depend on tissue biopsy to make an accurate diagnosis and proceed with further management. Advances in endoscopic neurosurgical techniques have made tumor biopsies safer in patients with pineal region tumors.[6,20] This technique can be performed under local anesthesia and obviates the need for open craniotomy and is especially useful in cases where the mass is deep seated.[23] It is a well-known fact that pure germinomas are not homogenous and might not show up on the small biopsy specimen which on an average is around 2 mm in its greatest dimension.[23,24] In this situation, even stereotactic biopsy has an acceptable sampling error and the minimization of this error depends on the expertise of the neurosurgeon in selecting the appropriate site of the biopsy. The stereotactic biopsy is not without its own risk: Wong et al have reported cases of acute reduction in intracranial pressure to zero after a ventricular endoscopic approach led to tumoral bleeding in the pineal region. They encountered this entity during a biopsy procedure and suggested a long subcutaneous tract, external ventricular drainage, and urgent radiation on the tumor as a treatment plan.[13]

According to the World Health Organization, germinoma represents a typical type 2 cell pattern tumor composed of germinoma cells mixed with lymphocytic infiltration that does not secrete melatonin.[25] The tumor is composed of large cells possessing round nuclei with prominent nucleoli and a glycogen-rich, clear cytoplasm.[26] The cells proliferate in a solid sheet-like arrangement. There is lymphocytic infiltration around the vascular stroma and the lymphocytes are T-lymphocytes.[24,26] Macrophages are seen in the tumor biopsies and a granulomatous inflammatory reaction sometimes overwhelms the tumor parenchyma. Case series state that the risk of sampling error is directly proportional to the extent of the coexisting granulomatous inflammation.[24] Pathologists should be aware of this phenomenon, because repeat biopsy in these cases have not really improved the diagnostic probability.[24] In such cases, tumor staining is useful in identifying the cells that are specific to these tumors.[26]

Placental alkaline phosphatase and the novel proto-oncogene c-kit (CD 117) are useful tumor markers for CNS germinomas.[27,28] Tumor markers are not specific enough to establish the difference in the histological types of GCTs.[25] There has been an attempt to identify more specific tumor markers that can accurately differentiate between pineal region tumors and identify pineal germinomas. Grimoldi et al raised the possibility of melatonin acting as a reliable marker for pineal region tumors as it is the major site of rhythmic production of melatonin.[25] They demonstrated that pure germinomas mostly do not secrete melatonin in a rhythmic fashion unlike benign neoplasms like pinealocytoma and pilocytic astrocytomas which may be helpful in the identification of germinomas.[25]

Since the biopsy material obtained via stereotactic biopsy is often small and GCTs are usually heterogeneous, the presence of nongerminomatous elements needs to be excluded by assaying the serum and the CSF for tumor markers like HCG and alpha fetoprotein (AFP). High levels of these markers are associated with more malignant GCTs, and these tumors are not as radiosensitive as pure germinomas which changes the management protocol of such mixed cell masses.[6] Mild elevation of HCG can be seen in pure germinoma, and this has been linked to the development of precocious puberty. The authors suggest that a level in serum or CSF greater than 50 mIU/mL is suggestive of nongerminomatous GCTs as pure germinomas seldom produce such high levels of the hormone.[6] In tumors with normal tumor marker levels, it is important to differentiate between germinoma and other pineal tumors, especially pinealoblastomas, as adjuvant treatment in absence of CSF metastasis is different for the two tumors.[4,13] This brings us back to the importance of tumor biopsy in the treatment algorithm of pineal germinomas.

CSF cytology helps in identifying the spread of a pineal germinoma through the ventricular system and the spinal subarachnoid region.[29,30] Spinal metastasis of intracranial germinomas occur in 10–20% of cases.[20] Tosaka et al have reported a case of spinal epidural metastasis that was diagnosed with the aid of MRI enhanced with GD-DTPA, but the CSF cytology was negative and led to inappropriate staging and inadequate treatment.[30]

Reddy et al reported that direct visualization of the third ventricular region may be more sensitive than MRI for evaluating the presence of suprasellar disease and appears to add more information.[6] As mentioned above, DI signifies suprasellar involvement and the presence of DI, in their series, was 100% predictive of suprasellar disease, even when MRI was negative for involvement of that region.[6]

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