Pineal tumors are rare and only limited series concerning pediatric patients can be compared in literature. This is true mainly for true pineal tumors in pediatric age considering that the Children Oncology Group enrolled only 34 patients [7], in age superior to three years old, 41 patients the Saint Jude Hospital[8], while a cooperative SIOP E study reported 131 patients trying to compeer clinical evolution, neuro-oncological treatment and bio-molecular and genetic difference [9]
All our cases were enrolled in the French Register for pineal region tumors [6] that concerned 891 patients recordered until the end of December 2021 : 316 cases (35%) were in pediatric age and 151 pediatric cases (16%) were treated in Lyon representing 47% of all pediatric cases.
This Register was created in Lyon at beginning with the first 22 cases, reported in the thesis of Science of the prof. Anne Jouvet+,that became a specialist of pineal tumors, and analyzed with electronic microscopy of [10].
It collected all national patients treated in all the twenty-six neurosurgical centers of France since the years 2000 and was declared to the CNIL in the year 2008 and definitively located in Lyon since 2010.
Our experience confirmed, according literature, that surgical mortality and morbidity for pineal tumor treatment was reduced in the last twenty years and surgical mortality was of only 1,8% in the French Register and of 1,5% in our experience [6].
The progress of microsurgical and anesthesiological techniques have permitted also to region tumor reduce the rate of post-operative sequels [11–13].
The surgical approaches have to be tailored in function of the volume of the lesion and the axis of the growth of the tumor also if surgeons choose the avenue with which they are more familiar. Our deep conviction is that each surgeon, that take in care pineal region tumors, should be familiar with different approaches to offer the best surgical alternative to each patient.
The endoscopic third ventriculostomy has permitted to manage hydrocephaly reducing the rate of complications related to the shunts, favoring also a histological diagnosis because, with the experience, pathologists became more performant to establish a precise diagnosis also in presence of small samples [6, 14, 15].
Used at the end of microsurgical removal, endoscopy can facilitate the visualization of residual piece of tumor in the blind corners improving the rate of total resection. In the pineal region many histological types are present and many of them need a neuro-oncological treatment and the complete removal represent a good prognostic factor.
We don’t think that the exclusive use of endoscopy have a large place for surgery of pineal region tumors for the potential risks of hemorrhagic complications specially when the dissection of the lesions is 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 endoscopic technique can be reserved to particular cases [16];
True pineal tumors concern 30% of cases pinealoblastomas, 52% 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 pynealocytomas only 1% of cases.
Looking at this histological repartition we can underlie that pinealocytomas are very rare in children and it is more frequent in young adults and only 6 cases were censored in the French Register, confirming their rarity. [17]
For benign lesions the surgical complete removal could guarantee the definitive cure and consequently, if the post-operative MRI showed a residual nodule, a new surgical procedure was indicated for us and there was no indication for a complementary chemotherapy or radiotherapy except particular situations [18]. The role of radiotherapy could be different in adults patients in which a redo surgery can be correlated with high surgical risks[19] .
Generally, for malignant tumors a total removal should be the goal but, in case of residual nodule, surgery should be discussed at the light of the possible surgical risks and at the light of efficacy of complementary treatments.
The prognosis of pinealoblastomas remains severe with an high rate of mortality as observed in our series of 18 pediatric cases treated in the last twenty years and specially in very young children confirming that age inferior to three years old represent a bad prognostic factor also in case of complete removal [20, 21].
The histological and bio-molecular knowledge have permitted to definite five sub group for pinealoblastomas with a different biological evolution considering the stratification of patients according age because patients younger of 3 years old represent 24% of cases while 59% of patients are aged between > 3 years and < 18 years old [17].
Patients with PB MYC/FOX R2 and PBRB1 were younger children and had a dismal prognosis. The group with PB-miRNA1 or PB-miRNA2 was found in older children or young adolescents with a more favorable prognosis [22] The genetic studies of our cases confirm the indications of the Tumor Consortium Study.
The stratification of patients in different subgroup has permitted to establish criteria of gravity of the disease and consequently the possibility to adapt therapeutical protocols to different degree of gravity of the disease with the hope that new drugs could improve clinical results specially for very young patients.
Germ-line mutations predispose to pinealoblastoma and De Kock et al have reported that DICER1 is an important susceptibility gene for pinealoblastoma and PB can be the expression of a germ-line mutation [23]
The genetic studies demonstrated that the extension of surgery was not always a significant factor for 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 and also if we agree with him, other reports showed no significant relationship between the total resection and the overall survival [25, 26].
Complete surgical removal of pinealoblastomas needs experimented surgeons because these tumors are hemorrhagic and it is important to avoid in very young patient severe sequels in the early post-operative period.
Our series of pinealoblastomas showed an overall survival in 27% of cases but all patients in an age inferior to 5 years old had a very dismal prognosis because all were dead. The median survival of our series was of 3,9 years with a range between 17 and 1 years.
Progression free survival reported in the recent literature in a series 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 chemotherapy without RT was ineffective to obtain remission in treatment of pinealoblastomas [9].
The high rate of mortality makes necessary to discover new drugs to improve the clinical results avoiding the risk of the brain irradiation if possible in very young patients.
A better stratification of patients should allow tailored treatments, especially for young children, and could represent the evolution of therapeutical strategies in a next future as preconized in literature. [17]
The PPT –ID are more frequent in adolescents and young adults patients in age of 33 years old and except for grade II with a total removal they need a complementary treatment to improve the survival [6, 21].
For Germ Cells tumors it is necessary to establish at beginning a precise diagnosis, or with the study of tumoral markers in the CSF and in the blood or with the help of a biopsy [28] [29]. It is important to consider the presence of a diabete insipidus that facilitates the discovery of a bifocal location. This situation was found in twelve patients (20%) of our series. A diabete insipidus in the exclusive pineal location is extremely rare [6].
In case of Germ Cell tumors surgery can be necessary or to treat hydrocephaly or, in cases in which, tumoral markers remain elevated in the blood and in the CSF after a treatment with chemotherapy, to remove non germinomatous components before radiotherapy [30].
In case of hydrocephaly consequence of the compression of the aqueduct of Silvius, ETV permits to cure hydrocephaly and also to realize a biopsy [1]. The rate of success diagnosis with the endoscopic technique is now of 87,9% [31] and of 95% for Schulz [1]. Kinoshita has preconized the necessity of samples from different region of the tumor to improve the precision of the diagnosis in cases of Germ Cell Tumor to discover non germinomatous components and to ensure adapted treatments [15].
We think that the endoscopic biopsy need sufficient material but we have to avoid multiple samples of material from different region of the tumor to avoid risks of severe hemorrhagic complications possible also with the use of a flexible endoscope [15].
In our series two patients needed a shunt after the failure of the ETV showing that the ETV alone was not always able to treat hydrocephaly.
Germ cells tumors has been treated with different protocols of chemotherapies following the indication of the French Society of Oncological Pediatry (SFOP) or of the International Pediatric Oncology Society (SIOP) associated with radiotherapy on the ventricular system with a boost on the tumor location.
The results of treatment for embryonal carcinomas, yolk stalk tumors and chorioncarcinomas depended by the effectiveness of chemotherapic program to reduce their volume but still now we had limited results because the rate of mortality remained still elevated [32].
The surgical treatment of these tumors was proposed after chemotherapy or radiotherapy to reduce the volume of the lesion but it was demonstrated that radiotherapy, producing a reaction of fibrosis, increased the surgical difficulties for a complete removal and also the rate of morbidity [33].
For Germ Cells 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) followed by involved field irradiation to 40 Gy. With a front line chemotherapy and the extended field of radiotherapy including the ventricles a 100% survival and a 89% of progressive free survival was reported by Khatua [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 a complete removal with a sub-occipital trans-tentorial approach were alive with a median survival of 5,7 years with a range varying from 1 year to 17 years [6].
Immature teratomas have on the contrary a rate of survival less important and the five years survival reported in literature varies between 35 and 40% [32].
Surgical treatment of glioma of the pineal gland is associated in our experience with good results [6]. In our opinion pineal gliomas represent essentially tectal plate gliomas and we think that all exophytic gliomas have to be operated with a direct surgical approach. Surgery is certainly debated but can play an important role for their treatment [6].
The limits of resection have to respect the plane of the aqueduct anteriorly, the plane delimited by the encroachment of the fourth nerves inferiorly and the colliculi or at least to respect one of the two colliculi if invaded by the tumor and if one is removed. The per operative recording of the auditory evoked potential is mandatory to reduce sequels and to favorite a large removal. The sixteen exophytic astrocytomas operated during the period of this study are all alive while the prognosis of more aggressive glioma is related to their malignancy instead of the complementary treatment as already reported [6].
Papillary tumors of the pineal region have been described in Lyon [10]. These tumors are not true pineal tumor but they belong to the pineal region. They origin from the sub-commissural organ of the third ventricle and their treatment need a total surgical removal to increase the chance of cure [10, 38] They are rare in children and we have censored in our experience only two cases that are alive, one needed an another program of chemotherapy following a total removal for a recurrence and now still in remission.
In literature only thirty cases were reported and consequently it is difficult to have a precise idea of the survival in children but it seems that total surgical removal represent a good prognostic factor to increase the survival and also to avoid sequels due to radiotherapy on an evolving brain but their incidence is rather in adolescent age and our patients were aged of ten years and thirteen years old [39].
Patients with a complete removal had a rate of survival in 63% of cases while patients with a partial removal or a biopsy had a worse evolution with a survival rate of only 26% of cases also after a complementary treatment with chemo and radiotherapy [6]
These results were reported by Févre-Montange while Poulgrain stressed the role of chemotherapy and radioptherapy on the rate of survival at five and ten years [40, 41].
The treatment of pineal ATRT tumors is very dismal because no patient of the four treated during the period from 1997 to 2020 were alive.
Pineal cyst represent benign lesions and their surgical treatment is necessary in children when an increased volume is responsible of a clinical picture, or when an intracystic hemorrhage is observed or when preoperative radiological diagnosis can orientate through a diagnosis of pinealocytoma [6]
The high number of pineal cysts operated in our series is related to an effect of recruitment consecutive to the expertise developed on the topic of tumors of the pineal region [6].
Of incidental discover pineal cysts are generally asymptomatic. Their diagnosis is increased with the advent of MRI studies and they have a benign evolution but in some cases, they can present an acute increase in volume and also an intra lesional hemorrhage responsible of a clinical aggravation and need a surgical treatment.
Their surgical treatment can be realized with a microsurgical technic or with an endoscopic approach and the presence of hydrocephaly, in adults as in children can justify the use of endoscopic removal [42, 43].
We know that pynealocytomas are very rare in children and the better knowledges of MRI permit us to establish a correct diagnosis and in consequence we limited the surgical indication and reserved surgery only in case with an important increase in volume or in case of acute intracystic hemorrhage.
The surgical approaches used are the infra tentorial supracerebellar, the sub occipital trans tentorial, the trans callosal trans fornical approach and many others [4, 42, 44–46].
The mini invasive techniques consist in a stereotactic aspiration, endoscopic marsupialization, endoscopic infra tentorial approach [47–49].
The use of ETV seems easier in presence of hydrocephaly while the direct approach is indicated in all cases with small ventricles. The use of neuronavigation can be useful with both techniques.
The endoscopic technique permits to treat in the same time the hydrocephalus and to realize the marsupialization of cysts or its complete removal through the ventricular system also if a complete removal can be risky for the hemorrhagic complications as reported by OI [43, 50].
It is always important the histo-pathological examination to confirm the diagnosis because in case of diagnosis of tumor, the complete surgical removal can be useful, if necessary, before the decision of an oncological treatment, if necessary, to give the best chances for a definitive cure.
Out of eleven cases operated in our series the sub-occipital trans –tentorial approach was used in ten ceses 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 benignity 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 is diagnosed in 10% of patients operated for a pineal tumor [6] and it is observed also in children that complain of irritability and tiredness mainly in school activity also if its incidence is lessen frequent than in adult patients because observed in only five % of our cases. The treatment of this syndrome is represented by the administration of melatonin.