Results of the treatment of pineal tumors in children: the Lyon experience

Pineal tumors are rare and their incidence is of 1% among all pediatric tumors of the central nervous system. Patient survival depends on the histology, the extension of the surgical removal, and the efficacy of the complementary treatment (chemotherapy and cranio-spinal irradiation), as well as the age of the patient. In this study, we analyzed 151 pediatric patients treated for pineal tumors from 1997 to 2020 in Lyon, France. All patients were recorded in the French Register of Pineal tumors, which has been centralized and maintained in Lyon since 2010. Our analysis shows that benign tumors have an overall positive prognosis with total surgical removal. Concerning pineal parenchymal tumors, pinealoblastomas have a poor prognosis , especially in children less than three years old. A new pathological classification system allows for a better stratification of patient risk within different groups of patients with pineal tumors. It is also important to note that the identification of DICER 1 syndrome in families with pinealoblastomas warrant further medical investigation. Patients with Germ Cell Tumors have more favorable outcomes, with a global survival rate of 87 % and a pure germinoma survival rate of almost 97%. When analyzing the prognosis of pineal gland gliomas, otherwise known as tectal plate gliomas, pilocytic astrocytomas had a promising prognosis. Otherwise, prognosis of other tectal plate gliomas are related to the grade of malignancy and the efficacy of complementary treatment. Lastly, papillary tumors need a complete removal for the best chance of survival, and Atypical teratoid/ rabdoid tumors (AT/TR) still have a bad prognosis, regardless of surgical resection. Our results show that, with regards to pediatric pineal region tumors, there are still areas in prognostic indicators that need to be improved. Similarly, these pathologies need to be treated via a multidisciplinary approach to improve a patient’s survival rate and their quality of life.


Introduction
Treatment of pediatric pineal tumors is complex because of the multiplicity of histological lesions that are found in this deep region. A multidisciplinary approach is necessary to define the best treatment strategy for each patient [1,2].
Each case requires a multidisciplinary approach that takes the clinical manifestations, the radiological characteristic of the tumor, its extension, the results of marker studies in the blood, and the CSF, and whether hydrocephaly is present, into account.
Hydrocephaly may require emergency treatment to decrease the risk of an evolving intracranial hypertension, and to prevent ophthalmological and neuropsychological sequelae [3,4].
In this article, we report the outcomes of pineal tumor treatment in a pediatric population from January 1997 to December 2020, in the Neurosurgical Pediatric Department of Lyon, France (Hopital Femme Mere Enfant).
The 151 cases were identified using the French Register of Pineal Tumors, a database containing 891 patients, including adults and children who were treated in twenty six neurosurgical centers around France [5].
In this database of 891 patients with pineal gland tumors, 316 patients (33%) are children. One hundred sixty-five of the 316 patients (54%) received treatment in different French centers other than Lyon, and 151 (46%) have been treated in Lyon. We considered the 151 Lyon cases for this report. Outcomes of the full French registry of 316 pediatric patients were reviewed in a previously published paper [6].

Materials and methods
All pediatric patients treated in the Department of Pediatric Neurosurgery in Lyon between January 1997 and December 2020 were considered. All these patients were identified for inclusion via the French Register of Pineal Tumors.
A total of 151 patients were eligible for the study with an age between 1 and 18 years old. The sex ratio was 1:2 males/females.
The symptomatology was characterized in 54% of cases by signs of intracranial hypertension with headaches and vomiting. Ophthalmological symptoms were present in 21% of patients. Endocrinological problems were associated in 5% of cases. In 18% of patients, the clinical manifestations were characterized by a more insidious onset of symptoms, including asthenia, tiredness, and gradual decline in academic performance.
All patients were studied with a cerebro-spinal MRI with and without gadolinium with angio-MRI sequences to study arterial feeders and venous structures. CT scans were occasionally used for patients receiving additional treatment at neighboring hospitals. None of the patients underwent angiography by the Seldinger technique for surgery.
Blood and CSF markers were studied in two different clinical scenarios: prior to surgical treatment for hydrocephaly, or during a lumbar puncture when the MRI did not show severe signs of intracranial hypertension. When clinical signs of intracranial hypertension prevented the patient from undergoing a lumbar puncture for the study of markers in the CSF, a multidisciplinary approach was taken. Specifically, the multidisciplinary Interregional Oncological Committee met to decide how to best perform a biopsy. The choice of the surgical technique for biopsy was primarily decided by the surgical team.
Hydrocephaly was present in 58% of patients and, in 38% of cases, an ETV and biopsy were required.
The pineal parenchymal tumors in the Lyon series represented 24 patients (15.8%). Eighteen cases were pinealoblastomas, and five cases were pineal parenchymal tumors of intermediary differentiation (2 grade II cases, 2 grade II-III cases, 1 grade III, 1 case with pinealocytoma).
Sixty percent of cases were female and 40% male. The age range varied from 18 months old to 18 years old, and the median age was 8.8 years.
With regard to the group of pineal parenchymal of intermediate differentiation, tumors were predominant in the female population. The only pinealocytoma was found in a male patient.
In two patients, metastatic disease was present at diagnosis. Surgical resection and removal was performed totally in 67% of the cases, and in it was subtotal in 27% of cases. A stereotactic biopsy was performed in a patient with metastatic disease in a poor clinical condition. He was ultimately started on a chemotherapy regimen, despite poor prognosis.
Germ cell tumors represented 39% of pineal tumors. Out of 59 patients, 36 had germinomas, ten had mature teratomas, two patients had immature teratomas, and 11 patients had mixed teratomas. Twelve patients presented with a bifocal tumor with an extension to the anterior portion of the third ventricle with infiltration of the pituitary stalk, or of the anterior portion of the floor of the third ventricle visualized on MRI.
Eighty-seven percent of patients were male and 13% were female. The median age was of 10.8 years old.
A biopsy was performed in sixteen patients with an endoscopic technique. During the same procedure, a third ventriculostomy was performed. All biopsied cases established a histological diagnosis.
In five patients, an open-approach biopsy was performed, and in three cases, a stereotactic approach was used. In one case, a neuronavigation system was used to perform the biopsy. For the other patients in the study, blood and CSF markers were enough to make the diagnosis. Two patients were treated for hydrocephaly with a VP shunt after the ETV.
All the 49 cases with a germ cell tumor with a pineal location could be reviewed for this study: twenty-three were pure germinomas, three immature teratomas, 11 mixed teratomas, and ten patients a mature teratoma.
Five patients (two immature teratomas and three mixed teratomas) were treated with surgery after chemotherapy, while ten patients with a mature teratoma were operated on after an endoscopic biopsy. Two cases and a direct approach at the diagnosis were in the other eight cases.
Sixteen patients in our series had pineal gland gliomas. The entirety of the French register had 37 pediatric pineal gland glioma cases. Pilocytic astrocytomas represented the most frequent histological type in our series. Other gliomas seen in the included cohort were gangliogliomas (two patients), and oligodendrogliomas (5 patients). Three patients were surgically treated for a pineal ependymoma.
Four patients were operated for an atypical teratoid rhabdoid tumor. Of these four patients, one patient was operated after an intratumoral hemorrhage, which resulted in severe cerebral enlargement with features of severe agitation. The other three patients were treated with a strong chemotherapy regimen. Of these three patients, in two cases, one case associated with a cranio-spinal radiotherapy.
Forty patients of the Lyon series presented pineal cyst, and 11 of these patients were operated on. Ten patients received a direct approach, and one received an endoscopic approach. All patients are survived surgical treatment and are still living.

Results
The rate of survival of pinealoblastomas was 22%. Nine patients (50%) of the eighteen patients with pinealoblastomas died after a surgical removal and a complementary treatment with chemotherapy.
In five patients younger than 5 years old, patients older than 4 years old associated with cranio-spinal irradiation, two patients were lost to the follow-up, and all the others died ( Fig. 1).
Of the five patients with pineal parenchymal of intermediate differentiation tumors, four were still alive after a complete removal and radiotherapy. One is still in remission after a salvage chemotherapy, and one died for a recurrence with metastatic disease. The only patient who received surgical treatment for a pinealocytoma was alive at the time of writing this article.
Thirty-six patients treated for a germ cell tumor located in the pineal region were alive with a median survival of 68.7 months (5.7 years). All these patients were treated with different protocols of chemotherapy, based on the French Society of Oncological Pediatry (SFOP) society guidelines and an additional targeting of the lesion via cranial irradiation.
In the group of patients that had bifocal lesions, two died and one patient was lost to follow-up. The overall survival rate for patients in the group of germ cell pineal tumors was 89% (Fig. 2).
Out of the four patients treated for an AT/RT, one underwent surgery while in a severe neurological condition and died 2 days after the surgical procedure of a cardiac arrest. Of the remaining three patients, two passed away after receiving large chemotherapy doses, and one passed away after receiving cranio-spinal irradiation.
Both patients with gangliogliomas are still alive. Of the five patients with oligodendrogliomas, four are known to be alive, and one patient was lost to follow-up.
All patients treated with surgery for a pineal cyst are alive.
We then analyzed the 75 alive patients who underwent complete follow-up at the last control in December 2021.
Of these 75 patients, 85% of the patients were able to live normally. Fifteen (percentage?) of patients developed minor sequelae, including mild motor deficits that did not impede on ability to ambulate, mild cerebellar symptoms, or visual symptoms that were subsequently documented in the ophthalmological routine control. We subsequently analyzed the academic performance of these living pediatric patients, considering it an important factor of quality of live.
Out of 75 school-aged patients, 63% were able to follow a normal program without problems; 15% presented mild difficulties with minor memory and concentration deficits but were able to follow a normal program. Twelve percent of patients needed an adapted school program.

Complication of surgical treatment
The surgical treatment of pineal tumors is associated with various complications. We observed that the rate of complications in the Lyon series was not statistically different from that observed in the entire French Registry series [5].
In the Lyon series, 1.5% of the mortality rate could be attributed to a post-operative embolic complication without a precise explanation. The rate of post-surgical hemorrhage was of 3.3%: three patients presented a subdural hematoma and two patients presented with an extradural hematoma. The subdural hematoma was evacuated surgically and drained with an external drain for 48 h. The extradural hematoma observed in two patients. Of these two patients, one needed surgical evacuation.
Infectious complications were observed in five patients (3.3%): sepsis in one patient, an abscess of the operative field in one patient, and meningitis in three patients.
Two patients presented with a skin flap infection that required an additional surgical procedure. The patients required removal of the bone flap in order to administer 6 months of antibiotic treatment, as required per the protocols of the Infectious Committee of our hospital (CLIN).
The rate of Parinaud syndrome was 7.3% in the post-operative period and decreased progressively to a rate of 0.7% during the follow-up at 6 months after the surgical procedure.
Four patients (2.6%) presented with diminished visual acuity. Seizures occurred in 7.5% of cases in the post-operative period and were subsequently treated with anti-epileptic drugs. After their resolution, as confirmed by a normal EEG and absence of symptoms, patients were weaned off after 6 months or 1 year, depending on the recommendations from our pediatric neurologists.
Five percent of patients that received surgical treatment presented with a pinealoprive syndrome. The incidence of this syndrome, however, could not be established due to lack of reports from other centers included in the registry. This syndrome, described by Claustra, exists in children and can be treated with the administration of melatonin.

Discussion
Pineal tumors are rare, and there are limited case series in existence, which makes comparing and understanding existing literature difficult. This is especially true for pediatric pineal parenchymal tumors. For example, the Children's Oncology Group enrolled 34 patients [7] older than age 3, 41 patients from Saint Jude's Hospital [8], and a cooperative SIOP-E study reported 131 patients comparing clinical evolution, neuro-oncological treatment, and bio-molecular and genetic difference [9].
In the French Registry study, all 891 included patients were part of the French Registry for pineal region tumors, and included cases recorded until December 2021: 316 cases (35%) were in pediatric age and 151 pediatric cases (16%) were treated in Lyon. Lyon therefore managed 47% of all pediatric cases indicated in this registry.
The Registry was initially developed in Lyon, and recorded the first 22 cases of pineal region tumors in the country. Specifically, the first 22 cases were reported and analyzed with electronic microscopy, as reported in Prof. Anne Jouvet's thesis, who later became an international specialist on the topic of pineal tumors [10].
Since its creation, the registry has collected national patient data from all twenty-six neurosurgical centers in France since 2000. It was declared part of the CNIL in 2008, and has since been formally based and managed in Lyon since 2010. This study of the Lyon data confirmed and matched findings in the current literature. Specifically, the study further confirmed that the surgical mortality and morbidity for pineal tumor surgical treatment has decreased in the last 20 years. At the time of this study, the surgical mortality rate was reported as 1.5% of patients in our Lyon-specific cases, and 1.8% in the entire French registry. Part of this decrease in mortality can be attributed to the advancement of microsurgical and anesthetic techniques, which have reduced the rate for secondary, post-operative surgeries when treating pineal region tumors [11][12][13].
Surgical approaches should be tailored to the individual case, taking into account the size and growth axis of the tumor. Surgeons are also encouraged to take into account, and use the techniques with which they are most familiar. With that said, it is our strong conviction that, in taking care of pineal region tumors, each surgeon should be comfortable with all available surgical techniques to offer the best approach to each individual patient. At Lyon, 70% of our patients underwent the sub-occipital transtentorial approach (6) because it allows for a larger space at beginning of the tumor dissection. It also allows for an easier control of the floor of third ventricle because it is located a shorter distance from the surface in comparison with the infratentorial approach.
The endoscopic third ventriculostomy procedure has improved the management of hydrocephaly by reducing the rate of complications related to the shunts. The procedure has also improved histologic diagnosis because pathologists have become more adept at establishing precise diagnoses through the analysis of smaller samples [6,14,15].
At the end of a microsurgical procedure, the endoscopy is used to facilitate the visualization of residual pieces of tumor in blind corners, therefore improving the rate of total resection. In the pineal region, many histological types are present. Many of the present histological types require a cross-disciplinary neuro-oncological treatment. The complete removal of the tumor is usually indicative of a good prognosis.
Despite the use of endoscopy for tumor resection, the potential benefits in pineal region surgery are not as convincing. Using endoscopy in pineal region tumors can increase the potential risks of hemorrhagic complications, especially when the procedures are done at level of the venous structures represented by the veins of the Galen, the basilar veins, and the cerebral internal veins. The exclusive use of an endoscopic technique can be reserved for particular cases [16].
Pineal parenchymal tumors make up 30% of cases pinealoblastomas. Fifty-two percent are PPT-ID and 18% are pinealocytomas of grade I [10], while in our series pinealoblastomas represent 75% of cases, pineal parenchymal tumors with intermediary differentiation represent 24%, and pinealocytomas make up only 1% of cases.
Looking at this histological distribution, it becomes clear that pinealocytomas are very rare in children and appear more frequently in young adults. Only one case is reported in the Lyon series, while 6 cases were found in the French Registry, which further supports their rarity [17].
For benign pineal parenchymal tumors, complete surgical removal could guarantee a definitive cure. Additionally, in cases where post-operative MRI showed a residual nodule, the implementation of new surgical procedures took precedence over complementary chemotherapy or radiotherapy, except in particular situations [18]. The role of radiotherapy could be different in adults patients in which a secondary surgery can be associated with high surgical risks [19].
Generally, for malignant pineal parenchymal tumors, a total removal should be the goal. However, in the case of a residual nodule, surgery should be discussed. In this conversation, surgical risks and benefits should be weighed, in addition to complementary treatments that can be proposed.
The prognosis of pinealoblastomas remains severe. There was a high mortality rate observed in our series of 18 pediatric cases treated in the last 20 years, especially in very young children. These results confirm that being less than 3 years of age is a bad prognostic factor, regardless if the tumor was completely removed [20,21].
Advancements in histological and bio-molecular understanding led to the development of five pinealoblastoma subgroups, which are defined based on their biological evolution and the age of the patient.
Patients younger than 3 years old represent 24% of cases while 59% of patients are between > 3 years and < 18 years old [17].
Patients with PB MYC/FOX R2 and PBRB1 mutations were younger children and had a very poor prognosis. The group with PB-miRNA1 or PB-miRNA2 mutations, found in older children or young adolescents, had a far more favorable prognosis [22]. Genetic studies of our cases also confirm the indications of the Tumor Consortium Study.
The stratification of patients in different subgroups has established a criteria to grade the severity of the disease. This grading classifications could possibly help update therapeutical protocols to treat patients based on the severity of their disease, with the hope that new drugs could improve clinical results, especially for very young patients.
Germ-line mutations predispose to pinealoblastomas and De Kock et al. have reported that DICER1 is an important susceptibility gene for pinealoblastoma development. PB can also be the expression of a germ-line mutation [23].
Genetic studies have also demonstrated that surgery was not always a significant factor for patient survival in patients with a localized disease and non-metastatic disease [8,9,24].
Tomita underlined the importance of a radical surgery for long term survival, though other reports showed no significant relationship between the total resection and overall survival rates [25,26].
The total surgical removal of pinealoblastomas needs to be performed by experimented surgeons because these tumors are hemorrhagic, and experienced hands are trained to avoid severe sequelae in young patients in the early post-operative period.
Pinealoblastomas cases in our series had an overall survival rate of 27%. Patients less than 5 years old, however, had a very poor prognosis and all cases resulted in death. The median survival of our series was of 3.9 years (postdiagnosis?), ranging from 1 to 17 years.
Progression-free survival reported in the recent literature in a series of 25 patients varied from 47.1%, 12.5%, and 0% in patients treated with cranio-spinal radiotherapy, all brain therapy, and focal RT [27].
The analysis of 135 children reported in the SIOP-E and the US Head Start pooled data showed that, in patients younger than 4 years of age, chemotherapy without RT was ineffective in obtaining remission in treatment of pinealoblastomas [9].
The high rate of mortality in pinealoblastoma patients makes it necessary to discover new drugs to improve the clinical treatment outcomes, while also avoiding the risk of the brain irradiation in young patients.
Improved stratification of patients could allow for individualized pharmacotherapy and treatment plans in young children, which would further the evolution of therapeutical strategies in the future [17].
PPT-ID are more commonly seen in adolescents and young adult patients, with an average age of 33 years old. Total removal is needed, except in grade II tumors, along with complementary treatment, in order to improve patient survival [6,21].
With regard to germ cell tumors, the initial establishment of a precise diagnosis is necessary, specifically through the implementation of tumoral markers in the CSF and blood, or via biopsy [28,29]. Additionally, the presence of diabetes insipidus in a patient could also help facilitate the diagnosis of a bifocal location. This scenario occurred in twelve patients, making up twenty (20%) of our series. Diabetes insipidus is a very rare sequelae in exclusively pineal tumors [6].
Germ cell tumors may require surgery in order to treat sequelae of hydrocephaly, or for when tumoral markers remain elevated in the blood and CSF after chemotherapy. Of note, it is important to remove non-germinomatous components before patients undergo radiotherapy [30].
In patients with hydrocephaly, patients often had resulting sequelae including compression of the aqueduct of Silvius. In these cases, ETV was used to correct hydrocephaly and also to perform a biopsy [1]. The success rate of making the correct diagnoses with endoscopic techniques is now reported as 87.9% [31] and 95% for Schulz et al. [1]. In cases of germ cell tumors, Kinoshita has noted the necessity of obtaining samples from different regions of the tumor in order to improve the precision of the diagnosis, especially in the diagnosis of non-germinomatous components and to ensure adapted treatments [15].
In our opinion, it is important to implement endoscopic biopsies in order to obtain sufficient sample sizes to ensure correct pathological diagnoses are made. However, it is important to avoid obtaining multiple samples from different tumoral regions to avoid severe hemorrhagic complications. These risks are equally high with the use of a flexible endoscope [15].
In our series, two patients required a shunt after a failure of ETV treatment. These outcomes suggested that ETV alone was not always able to treat hydrocephaly.
Germ cell tumors have been treated with different types of chemotherapies, depending on society protocols. Indications from either the French Society of Oncological Pediatry (SFOP) or of the International Pediatric Oncology Society (SIOP) were used. Both focused on radiotherapy on the ventricular system with a boost of irradiation directly on the tumor.
The outcomes of patients after treatment for embryonal carcinomas, yolk stalk tumors, and chorioncarcinomas depended on the effectiveness of the selected chemotherapic program. Specifically, treatment success depended on their ability to reduce tumor volume. It is important to note, however, our results in studying these outcomes remained limited in this study because the rate of mortality remained still elevated among patients with these tumor types [32].
The surgical treatment of these tumors was proposed after chemotherapy or radiotherapy to reduce the volume of the lesion. However, it was demonstrated that radiotherapy, producing a reaction of fibrosis, increased the surgical difficulties for a complete removal, along with an increase in the rate of morbidity [33].
For germ cell tumors, the French Society of Pediatric Oncology and the European SIOP CNS GCT-96 and the Japanese Cooperative Group studies [34] adopted a strategy with an upfront chemotherapy (platinum based) therapy, followed by involved field irradiation to 40 Gy. With a frontline chemotherapy regimen and the extended field of radiotherapy including the ventricles, a 100% survival rate and a 89% of progressive-free survival was reported by Khatua et al. [35].
For mature teratomas, surgery is the only treatment with a rate of survival that varied between 80 and 100%, as reported in literature [14,36,37].
All our cases treated with surgery with a sub-occipital transtentorial approach were alive, with a median survival of 5.7 years, ranging between 1 and 17 years [6].
Immature teratomas have, on the contrary, a worse rate of survival less and the 5-year survival rate reported in literature varies between 35 and 40% [32].
Eleven patients had mature teratomas, 8 of which had an increased volume. Their treatment included complete surgical removal. In this group, eight patients are alive, two patients died, and one patient was lost to follow-up (6).
Immature teratomas had more severe outcomes: of 16 patients, only 7 patients lived, five patients died, and four patients were lost to follow-up (6).
Surgical treatment of glioma of the pineal gland is associated, in our experience, with more favorable outcomes [6]. In our opinion, pineal gliomas represent essentially tectal plate gliomas and all exophytic gliomas should have to be treated with a direct surgical approach in order to perform a resection that is as large as possible. Surgery is certainly debatable, but can play an important role for their treatment [6].
The plane of resection is limited by the plane of the aqueduct anteriorly, the plane delineated by fourth nerve encroachment inferiorly, and the plane of the colliculi. Of note, at least one colliculi must be respected during surgical treatment if one is invaded by tumor and subsequently removed. The perioperative recording of auditory potentials is essential to reduce sequelae and to increase more favorable outcomes. Sixteen exophytic astrocytomas were operated on during this study. The results showed that all patients were alive at time of analysis. The prognosis of more aggressive gliomas, however, was related to their malignancy, rather than to their complementary treatment [6].
Papillary tumors of the pineal region have been described in Lyon [10]. These tumors are not true pineal tumors, but they are located in the pineal region. They originate from the sub-commissural organ of the third ventricle, and their treatment requires a total surgical resection to increase the chance of cure [10,38]. They are rare in children and we have identified, in our experience, only two cases that are alive. One of these two patients needed another program of chemotherapy following a total removal for a recurrence, and is still in remission at the time of writing this article.
In the literature, only thirty cases of papillary tumors of the pineal region have been reported, and it is therefore difficult to understand the progression and prognosis of these tumors in pediatric populations. However, it is likely that complete surgical removal is a variable indicative of a good prognosis in these patients. Complete surgical removal increases survival, while also preventing sequelae related to radiotherapy on a developing brain. The ages of these patients in our cohort ranges between 10 and 13 years old [39].
The patients that had a complete removal of the tumor had a survival rate of 63%. This was better than the survival rate of 26% seen in patients with partial removal or biopsy, regardless if they also received complementary chemo and radiotherapy treatment [6]. These results were reported by Févre-Montange. On the contrary, Poulgrain stressed the role of chemotherapy and radiotherapy on the rate of survival at 5 and 10 years [40,41].
Outcomes of pineal ATRT tumors are very poor. In our sample from 1997 to 2020, none of the four patients treated survived.
While pineal cysts are benign lesions in children, surgical removal is necessary when they occupy increased volume and become symptomatic. Surgery is also indicated in cases of intracystic hemorrhage, and when preoperative radiological diagnosis is unclear [6].
There was a high case number of surgically treated pineal cysts in our case series. This high case number can be attributed to better recruitment of patients that stems from a better understanding of pineal region tumors [6].
Incidentally discovered pineal cysts were generally asymptomatic. Incidental diagnoses of pineal cysts have increased with the advent of MRI studies. Though they tend to have a benign evolution, they can sometimes acutely increase in volume and become symptomatic. They can also cause an intra-lesional hemorrhage during surgery which leads to clinical aggravation.
Surgical treatment can be performed via a microsurgical technique or via an endoscopic approach and the presence of hydrocephaly. Endoscopic removal can be justified in adults and in children as necessary [42,43].
It is now understood that pinealocytomas are very rare in children. The improvement of MRI technology also allows us to establish more accurate diagnoses and limit surgeries. Surgical treatment can therefore be reserved for cases of increased volume or in cases of acute intracystic hemorrhage.
The use of ETV is more simple in the presence of hydrocephaly, while the direct approach should be used in all cases with small ventricles. The neuronavigation technique can be useful in both approaches.
The endoscopic surgical technique permits hydrocephalus to be treated at the same time as the marsupialization of cysts. It also allows for the complete removal of tumors through the ventricular system. It can also be used if hemorrhagic complications are likely, as reported by OI [43,50].
It is always important to perform the histo-pathological examination to confirm the diagnosis. Tumor type changes treatment approach. Complete surgical removal can be useful prior to the deciding oncological treatment, and provides the best chances for definitive cure.
Out of eleven cases operated in our series, the sub-occipital transtentorial approach was used in ten cases and the endoscopic removal in one case.
As already reported [3,4], we prefer the sub-occipital transtentorial approach for the advantages to expose and to work in this region under the venous arch represented by the basilar veins and the Galen veins. The benign nature of the pathology explains the high rate of survival observed in our experience [6].
After the surgical treatment, it is also important to recognize the post pinealectomized syndrome that was studied and described in Lyon by Claustra and Chazot [51]. This syndrome is characterized by headaches, fatigability, behavioral troubles, and anomalies of the circadian rhythm with sleep disturbances. This syndrome was diagnosed in 10% of patients operated on for a pineal tumor [6], and it is observed also in children that complain of irritability and tiredness, mainly in school activity. Its incidence is also less frequent in children than in adult patients as they were only present in 5% of our cases. The treatment of this syndrome is the administration of melatonin.

Conclusions
The surgical treatment of pineal lesions is possible in experienced hands, and has a low rate of harmful sequelae as demonstrated by the quality of life of patients that underwent surgical treatment. At times, it can be difficult to differentiate between disease-related sequelae or sequelae resulting from surgical/chemotherapeutic/radiological treatment.
Considering the diversity of pineal tumors in pediatric patients, it is important to implement a multidisciplinary approach to treatment to implement the best strategies for cure and improvement of quality of life in this group.
At the time of presentation, it is important to obtain a precise and accurate diagnosis that will subsequently dictate the next therapeutical steps for each patient. For example, it is important to avoid surgical treatment of germ cell tumors or some malignant neoplasms, which should be treated with chemotherapy prior to surgery. On the other hand, surgery is imperative for benign lesions that are symptomatic, while taking care to take certain steps to reduce post-operative sequelae and post-surgical morbidity.
The decisional and diagnostic tree also has to take the age of the patient into account because certain tumors are more likely in certain age groups. For example, in very young patients, we are more likely to consider PNETs, pinealoblastomas, teratomas, or ATRT tumors. In adolescent or young adult patients, pineal parenchymal tumors with intermediate differentiation, pinealocytomas, or gliomas are more likely to be on the differential. It is also important to take all tests and biopsies into account before deciding on definitive treatment options.
Pinealocytomas are very rare in children, while pinealoblastomas are more frequent. It is important to note, however, that they represent less than 1% of childhood brain tumors.
These tumors are typically treated via surgery, chemotherapy, and radiotherapy. Despite the various treatment modalities indicated, being less than 3 years old confers a poor prognostic risk.
For germ cell pineal tumors in presence of elevated markers, chemotherapy and radiotherapy are the best treatment. In cases of non-elevated markers and the absence of ventricular dilatation, a biopsy with a direct approach or in stereotactic condition should be performed [14].
In the case of non-elevated markers with a ventricular dilatation, an ETV with biopsy can be considered [52].
Genetic studies are also essential in order to establish new protocols of treatment with tailored chemotherapies and adapted cranio-spinal radiotherapy for pineal ATRT, pineal PNET, pinealoblastomas, and papillary pineal region tumors.
Surgery has an important place in the treatment of benign lesions. The approach of surgical treatment of pineal region tumors has to be adapted and to take into account the axis of development and the growth of the tumor.
A multidisciplinary discussion is vital to the successful treatment of pineal tumors, and improves survival rates while decreasing long-term side effects, ensuring satisfactory survival curves.