PICCCs are extremely rare and represent only 0.05% of all brain tumors in Japan (4
). A statistical analysis report published by the Committee of Brain Tumors Registry of Japan indicated that the incidence of choriocarcinoma was 3.2% (36 cases) out of 1127 primary intracranial GCT cases (5
). Additionally, Matsutani et al
analyzed 153 cases of histologically verified intracranial GCTs and revealed that the incidence of choriocarcinoma was 3.3% (3
). Due to this extremely low incidence, the majority of publications refer to case reports (6
), and few studies have compared the treatment and prognosis (1
). Matsutani et al
classified intracranial GCT into three therapeutic groups: those with good, intermediate and poor prognoses. PICCCs were classified into the poor prognosis group, and this group required more aggressive chemotherapy and radiotherapy (3
). A recent review article presented an algorithm for diagnostic evaluation and treatment of pineal or suprasellar tumors (12
). The author suggested that PICCCs require combinational therapy comprising chemotherapy, radiotherapy and resection. However, there is currently no clear national consensus for the optimal treatment of PICCCs.
Shinoda et al
reviewed 66 PICCC/GCTs with high β-HCG levels and revealed that their median survival time and their one- and two-year survival rates were 22 months, 61.2% and 49.8%, respectively (1
). Among these 66 patients, 34 (52%) succumbed within one year of diagnosis and 14 (21%) succumbed within one month of diagnosis. Early mortality is commonly associated with tumor hemorrhage. This suggests that the prognosis of these patients may be improved if the initial treatment focuses on the prevention of tumor hemorrhage.
To minimize early mortality arising from tumor hemorrhage, we planned the following treatment regimen. First, we did not conduct a tumor biopsy for pathological confirmation. β-HCG is regarded to be more characteristic of β-HCG-secreting tumors. Markedly elevated β-HCG levels are strongly suggestive of choriocarcinomas, while mild elevations can be observed in other GCTs of syncytiotrophoblastic giant cells (1
). In a study by Matsutani et al
, all patients with pure choriocarcinomas or mixed GCTs with a choriocarcinoma element had highly elevated serum β-HCG levels of >2,000 IU/l, while GCT patients without a choriocarcinoma element had serum β-HCG levels of <770 IU/l (3
). The serum β-HCG level in our patient was >1,0147 mIU/ml. The patient had a tumor arising from the pineal region with hemorrhage, hydrocephalus and a history of progressive consciousness deterioration. A biopsy was not conducted due to the limited access and high hemorrhagic risk. We diagnosed the tumor as PICCC based only on extremely elevated β-HCG levels, and could prevent tumor hemorrhage by biopsy. Secondly, we selected synchronous chemotherapy and radiotherapy as the first-line treatment. Sakurada et al
reported that tumor hemorrhage occurred when radiotherapy was conducted as an initial treatment (13
). Shinoda et al
stated that initial biopsy and radiotherapy may lead to tumor hemorrhage in PICCCs (1
). Thus, we determined that it was dangerous to start treatment with radiation alone. Kageji et al
reported a case of successful neoadjuvant synchronous chemotherapy and radiotherapy for disseminated PICCC (8
). The patient underwent induction chemotherapy in parallel with radiotherapy as the initial treatment. Following radiotherapy and the second course of chemotherapy, the patient underwent radical tumor surgery. There was no evidence of hemorrhage during neoadjuvant treatment. Based on this, we immediately started initial treatment comprising synchronous chemotherapy and radiotherapy. The patient did not undergo fatal events by hemorrhage during synchronous therapy, and once the first course of synchronous chemotherapy and radiotherapy was complete, the previously observed hemorrhage had disappeared. Thirdly, we did not attempt to remove the remaining mass. The patient had a tumor arising from the pineal region, and due to the number of neurovascular structures in this area, it is a surgically inaccessible area of the brain (14
). Despite the fact that the tumor hemorrhage had disappeared following the first course of treatment, the hemorrhagic risk of PICCC remained. Chan et al
reported a case of successful treatment with chemotherapy and radiotherapy without surgery (15
). We planned three consecutive courses of chemotherapy without surgery. The tumor mass was reduced by 63% (14x12 mm), and the patient’s abnormal neurological symptoms were fully recovered.
To date, the majority of the literature suggests that intensive chemotherapy, radiation and tumor resection offer the best chance of treating PICCCs. We agree with this opinion; however, we suggest that a personal approach to prevent early tumor hemorrhage is the most important factor.
Although PICCCs are rare, their propensity for fatal hemorrhage and extraneural/CSF metastasis results in a poor prognosis. Our patient exhibited severe consciousness disturbances and a high level of serum β-HCG. Since the initial imaging study demonstrated a tumor mass with hemorrhage in the pineal region, we immediately began synchronous chemotherapy and radiotherapy. Subsequently, our patient underwent three courses of chemotherapy, each comprising the same ICE regimen. The residual tumor mass was not resected due to limited access and hemorrhagic risk. Nearly two years following the initial diagnosis, the patient is alive without tumor progression and with normal neurological functions.
In conclusion, we reported a rare case of PICCC. We diagnosed our patient with the aid of serum β-HCG level without biopsy, and immediately started induction therapy comprising synchronous chemotherapy and radiotherapy. Without surgery, we delivered ICE chemotherapy as consolidation treatment. These treatments led to tumor regression and marked improvements in the patient’s signs and symptoms. Nearly two years post-diagnosis, follow-up imaging has demonstrated no tumor progression. This is the first report of successful synchronous chemotherapy and radiotherapy, followed by three courses of consecutive chemotherapy, to treat a patient diagnosed with PICCC by focusing the initial treatment on the prevention of tumor hemorrhage.