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

Treatment

Pineal germinomas are a rare occurrence, and large prospective randomized trials to define a treatment strategy are not yet available.[4,8] The treatment protocols vary from center to center but are primarily radiation based as this tumor is exquisitely radiosensitive, and 90% of patients with pure intracranial germinomas can be treated successfully by radiation therapy.[31] The dose of radiation that causes a dramatic reduction in the size of the germinomas starts as low as 600 cGy; complete disappearance of the mass lesion is seen with doses ranging from 1600–3300 cGy.[32] As mentioned above, these tumors sometimes contain other nongerminomatous elements that are more radio-resistant, hence the minimum effective dose of radiation is difficult to determine and has been maintained well above 3300 cGy to accommodate the mixed type of tumors.[32]

Prior to the advent of microsurgical techniques, clinicians found empiric radiation therapy to have a more positive risk benefit ratio as compared to other treatment modalities. In current practice, however, empiric radiation therapy is no longer considered to be justified and patients are made to undergo stereotactic biopsy of the mass to obtain a definitive diagnosis.[20] Once a diagnosis is confirmed, patients are typically divided into two groups depending on the presence of a localized disease or disseminated disease, as determined by neuroimaging or positive CSF cytology.[6] Patients with localized disease are administered involved field radiation only and those with disseminated disease at diagnosis receive both involved field and whole brain or craniospinal radiation.[6,33] The detection of DI with biopsy-proven pineal region germinoma should assign patients to a disseminated disease category even in the absence of neuroimaging findings as mentioned in the diagnosis section.[6]

The radiation dose that is recommended for treatment is greater than 50 Gy to the primary site. Major sites of recurrence for these tumors are the suprasellar and ventricular walls, hence radiation should cover these sites.[15,34] Radiation is associated with long-term side effects such as deteriorated endocrinological status, impaired growth, and intellectual deterioration.[34] The severity of these effects seem to correlate with the age of the patient at the time of the treatment and the dose and field of treatment; younger patients with disseminated disease suffer from more side effects.[6] Therefore, the radiation fields and doses have been reduced to decrease these side effects.[34] All patients are given adjuvant chemotherapy with a cisplatin-based regimen in an attempt to decrease the total radiation dose.

Isolated case reports have found intracranial germinomas to be chemosensitive, but the use of chemotherapy alone is reported to be associated with increased incidence of relapse that required salvage radiation for complete eradication.[6,35] Hupperets et al have reported a case of intracranial GCT that they successfully managed with cisplatin in combination with etoposide and bleomycin and avoided the use of radiotherapy. The case report only follows the patient up to 15 months from tumor eradication, and the authors agree that longer duration of follow up needs to be studied before this strategy is widely applied.[36] The chemotherapeutic agents found to be effective are cisplatin, bleomycin, vinblastine, and etoposide.[6] The chemotherapeutic drugs mentioned above have significant side effect profiles of their own. A treatment regimen consisting of cisplatin, vinblastine, and bleomycin (PVB) or bleomycin, etoposide, and cisplatin (BEP) avoids the use of alkylating agents and the resulting sterility, but they are still accompanied by renal and auditory toxicity.[37] Other long-term complications from chemotherapy have been recognized, such as secondary leukemia (eg after cisplatin and or etoposide therapy), and solid tumor like granulocytic sarcoma, also known as chloroma or myeloblastoma (after a cisplatin, etoposide, and bleomycin regimen).[38] Leukemia that follows an alkylating agent regimen (eg cisplatin) are typically M1 or M2 acute myeloid leukemia types and mostly occur after an average interval of 5 to 7 years, whilst the topoisomerase containing regimens (eg etoposide) mostly cause M4 or M5 phenotype after 2–3 years following treatment.[38] Pinkerton et al studied a treatment protocol that substituted carboplatin for cisplatin that had similar efficacy but with lesser nephrotoxicity and ototoxicity.[37] However, some form of radiation is always suggested to maintain long-term control for these patients.[6] As a result, chemotherapy has the advantage of decreasing the total dose of radiation, but the use of chemotherapy is also associated with drug-related side effects and increased hospital stay and treatment costs.

Radiosurgery is now considered to be another treatment option, along with chemotherapy and radiation, for germinomas.[34] The protocol that was studied by Endo et al included stereotactic gamma knife radiosurgery using 10–12 Gy followed by whole ventricular irradiation using 24 Gy in daily fractions of 2.0 Gy to the tumor bed. They suggested that radiosurgery increased the therapeutic ratio by reducing the irradiated volume of the surrounding brain tissue. Their study protocol did not include histological verification as an inclusion criterion as they believed that the benefit of not increasing the risk of dissemination by surgical manipulation surpasses the risk of misdiagnoses. They documented a decrease in treatment dose and length of stay and even suggested that this could be done on an outpatient basis.[34] The use of radiosurgery is questionable in disseminated disease.

Hydrocephalus is a serious complication of pineal region tumors and has to be managed appropriately. Prior to the advances in neurosurgery, ventricular-peritoneal shunts were placed to relieve the increased intracranial pressure. Ventriculoperitoneal (VP) shunts can lead to peritoneal metastasis of primary GCTs, which means that patients with VP shunts required follow-up CT scans of the abdomen to detect metastatic disease.[38,39] Neurosurgeons have the ability to safely perform endoscopic third ventriculostomy in patients with hydrocephalus from pineal region germinomas.[6] Ventriculostomy is considered a good alternative to VP shunt to relieve the hydrocephalus, and it does not carry the risk of peritoneal metastasis in the future.[39] However, the risk of infections is a matter of concern after ventriculostomy procedures. There are two isolated case reports of spontaneous regression of pineal germinomas that have been attributed to a patient's immune response. The cases have been likened to similar cases seen with testicular seminomas.[40]

Our patient received a combination of craniospinal radiation and chemotherapy. The germinoma responded well to the above regimen as resolution of the tumor was evident on subsequent follow-up imaging studies.

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