Clinic And Pathology Characteristics Research Of Pineal Region Mixed Germ Cell Tumor

ObjectiveIntracranial germ cell tumors usually locate in the pineal region, encompass various histological subtypes, and their optimal management has been the subject of debate. Pathological component of Mixed germ cell tumors (M-GCTs) is complex, need accurate pathology diagnosis to guide treatment, A effective treatment could improve patient survival rate, and even improve the patients quality of life. Our research based on improving the treatment of M-GCTs, Approaching distribution characteristics of pineal region M-GCTs by imaging findings and pathological components, to explore the growth pattern. And analyze the clinical features and therapeutic regimen of M-GCTs to summarized the the best treatment path of M-GCTs.Part I Research of pathological characteristicsMethodsTo retrospectively investigate 15 cases of pineal region mixed germ cell tumors specimens in our hospital from January 2000 to September 2010. Re-takening biopsy specimen and do HE(hematoxylin and eosin) staining for the controversial pathologi-cal specimens.And observe the percentage of each tumor components with the origi-nal biopsy specimens, study athology observed di-stribution. It is estimated the share of various components in the tumors. We count the tumor cells with naked eye. The data indicated that the general distribution of the pathological elements. Indicato rs of immunohistochemical staining for diagnosis (Department of pathology provided )are as follows:PLAP (human placental alkaline phosphatase),AFP(alpha fetoprotein),β-HCG(β-human chorionic gonadotropin),CK(cytokeratin),CD117(c-kit stem cell rec eptor).Result1,pathology:To rechecked one paraffin block found new components. Table 1 showed the components of the tumors and the composition ratio of these 15 patients.13 patients included germinoma component,9 cases had teratoma component, 6 patients with embryonal carcinoma,4 cases with choriocarcinoma,7 contained yolk sac tumor component, and 3 cases with rhabdomyoma. Germinoma could be found at the tumor edge of 7 cases. In 10 patients, germinoma mixed other components with each other or surrounded by other components.2% The proportion characteristics of the tumor components observed as following (table 1-1):Teratoma can be accounted for larger proportion in the mixed tumors, Specimens containing teratoma component in 9 cases, Their contents almost are more than 30%, in 13 patients with germ cell tumor component samples, Content of less than 30% in 8 cases,7 cases less than 20%,7 specimens with high malignant components, Content is more than 30% in 8 patients,50% in 6 cases.3,immunohistochemistry:13 cases of 15 patients showed positive staining for PLAP,11 for AFP,5 forβ-HCG,12 for CK,4 patients with CD117 (c-kit) positive expression. All 6 cases that contain embryonal carcinoma showed positive staining CK (100%),6 in 7 patients with yolk sac tumor showed positive staining AFP (85.7%), all 5 case that contain immature teratoma showed positive staining AFP (100%), with in,3 of 4 cases with choriocarcinoma specimens showed positive stainingβ-HCG(75%). Three cases contained rhabdomyosarcoma component showed positive staining for vimentin, eurofilament (NF).4,All tumors were located in the the suprapineal recess which was enclosed by arachnoidal envelope of Galen vein.Intraoperative findings relationship between the tumor and pineal is Closed, they usually stuck together, Not even see a complete form of the pineal glandConclusions1,Most of mixed germ cell tumor with highly malignant germ cell tumor component, Germinoma and teratomas combination is two ingredients of most frequently appear in mixed germ cell tumors. There is a high proportion of teratoma components.2,Germinoma components often appear in the tumor edge, Other tumor elements interspersed each others, no specificdistribution of inclusion.3,Pineal mixed germ cell tumor originated in the pineal gland, and most likely generate from primordial germ cells. Rhabdomyoma may be derived from the germ cell component, Can be grouped into a class of germ cell tumors.Part II Analysis of the clinical features and treatmentMethodsCollected medical records of 15 cases of pathologically confirmed patients with mixed GCTs between January 2000 to september 2010. All microsurgical resection of the tumor were by the occipital transtentorial (Poopen) approach under general anesthesia and receive chemoradiation. the lesion of 15 patients were total removaled, and get complete tumors specimens. Materials of biopsy is that drawn much more situs from the tumor.Explicitly for the diagnosis of mixed germ cell tumor. Retrospe ctive analysis included:age distribution, morbidity, the proportion of patients of each ages, gender distribution, clinical manifestations, imaging findings. Summarize onset time of symptom in patients, Surgery, chemotherapy, radiotherapy outside our hospita 1 and resection of tumors. Compared the serum tumor markers level of pretherapy and post-treatment,tumor markers indicators is as follow:serum carcinoembryonic antige n(CEA) normal reference range is 0～5.0ug/L,alpha-fetoprotein(AFP) normal referenc e range is 0～8.1 ug/L, human chorionic gonadotropin (β-HCG) normal reference range is 0～3IU/L. Using SPSS statistical software version 13.0 Life table for follow-up results of survival analysis, preoperative and postoperative tumor markers to do paired samples t test.Results1,This group contain 15 patients, all male, age 8 years to 24 years, mean age is 16.3 years old,3 cases is in 8 to 10 years group(20%),9 cases in 11 to 20 years (60%),3 cases in 21 to 24 years group(20%).2,The clinical manifestations and therapy outside our hospitalThe major clinical manifestations:11 intracranial hypertension cases(73.3%), Parinaud's sign were observed in 10 patients (66.7%), decreased vision in 5 patients (20%), diplopia in 2 cases (13.3%), Auditory impairment 2 cases, Ataxia in 4 (26.7%), fatigue, somnolence in 2 cases, Clinical Symptoms duration is 5 days to 1 year. One of the cases come to us because of polyuria. There are not patients with precocious puberty.Therapy outside the hospital:2 patients had ventriculoperitoneal shunt due to hydrocephalus,2 patients received ventricular puncture drainage because of acute intracranial hypertension,3 patients who underwented external radiation therapy,2 cases with ordinary radiation,2 cases with gamma knife treatment, one of which patients recurrence after gamma knife radiotherapy of ordinary again.3,Neuroimaging:combine brain CT and MRI,7 patients had significantly expanded ventricular system, 10patients with cysts,12 patients had calcification,4 cases had lipids. All MRI showed mixed signals, slightly low signal intensity on T1-weighted imagess and high intensity on T2-weighted images, and good heterogeneous enhancement, but there was slightly different,9 cases less heterogeneo us enhancement,6 cases which include highly malignant components show more apparent mixed signal enhancement. Sagittal Images found 6 cases showing round or elliptic shape with smooth edges, The shape of 9 cases which include teratoma component was irregular, nodular or lobulated.13 cases were still capable to resolution quadrigeminal form, quadrigeminas of 2 cases is disappeared.4,Tumor marker test results:10 patients do tumor marker test, all patients'CEA is normal,3 patients'all tumor marker test is normal,7 patients is abnormal.5 patients only AFP heightened,1 patient onlyβ-HCG heightened,1 patients' AFP andβ-HCG heightened at the same time,3 patients' AFP is more than 300 ug/L. Decrease of tumor markers in all patients after our surgery, NO 10 patients' AFP is as high as 101230ug/L before surgery, but it is down to 64.8ug/L after tumor resection. there is no significant statistical difference between two groups.5,Treatment and follow-up results:All patients were removed the tumor by Poppen approach, and received neoadjuvant chemoradiation after surgery.Follow-up 15 patients,12 patients survived,3 patients were dead.1 died of Systemic failure after 5 month,2 patients were died of tumor recurrence in 16 months and 40 months separately after surgery, all of these 3 patients' tumor contain highly malignant components. Overall 1-year survival in this group was 93%, 3 year survival rates were 85%,73% 5-year survival. Patients who's tumor mainly contain germinoma and teratomas (n=9),1-year,3-year,5-year survival rate all were 100%, containing highly malignant components patients (n=6) 1-year survival rate 83%,3-year is 67%,5-year is 48%. The two groups were statistically significant differences. This group recently overall survival rate was higher than literatures', 5-year survival rate was slightly higher or unchanged forward in the literature. Survival time of patients who's tumor mainly contain germinoma and teratomas is significantly higher than those reported in the literatureConclusions1. Pineal mixed germ cell tumor is common for man in the adolescent stage.2.Clinical manifestations of pineal mixed germ cell tumor is atypical, short duration,early misdiagnosisrate is high, such as cranial CT and MRI imaging ha ve high diagnostic value. Serum tumor markers AFP, HCG must be examined to improve the diagnostic rate.3. Teratomas and highly malignant tumors components were normal ingredients which often contained, they were not positive to radiotherapy. So Mixed germ cell tumor line is not suitable for radiation therapy before surgery 4.Total removal of tumor can obtained accurate pathology diagnosis, it could effectively guide the adjuvant treatment, Significantly improve the pineal region mixed germ cell tumor patients'survival time. For patients who's tumor mainly contain gerinoma and teratomas, survival time of total resection combined following chemoradiation was significantly better than chemoradiation first and secondly Resection residual focus. And total resection combined following chemoradiation had a higher survival rate in highly malignant components patients'..It is imperative to preserve the neurological function in operation when utmostly removal the lesions so that radiotherapy and chemotherapy can be more effective. Total removal of tumor surgery can significantly improve survival time of patients. If surgical technology, total resecting tumor as far as possible. Choosing a suitable therapeutic regimen is helpful for patient. Combining autologous hematopoietic cell rescue may improve prognosis and quality of life.5.Mixed germ cell tumor major component determine its degree of malignancy, survival time of patients who's tumor mainly contain germinoma and teratomas were significantly longer than those containing highly malignant components patients.6. Summarize the compatible treatment path of mixed germ cell tumor:If pineal region occupying were found in young male patients'images, they should check serum tumor markers and cytology or tumor markers of CSF. If the results were positive, it could be diagnosed as mixed germ cell tumor with highly malignant germ cell tumor components or highly malignant germ cell tumor, they need Radiotherapy and chemotherapy after surgical removal of the tumors. If young males with negative tumor markers, they could be treated as germinoma.